Abstract

Histone deacetylase (HDAC) 10, a class II family, has been implicated in various tumors and non-tumor diseases, which makes the discovery of biological functions and novel inhibitors a fundamental endeavor. In cancers, HDAC10 plays crucial roles in regulating various cellular processes through its epigenetic functions or targeting some decisive molecular or signaling pathways. It also has potential clinical utility for targeting tumors and non-tumor diseases, such as renal cell carcinoma, prostate cancer, immunoglobulin A nephropathy (IgAN), intracerebral hemorrhage, human immunodeficiency virus (HIV) infection and schizophrenia. To date, relatively few studies have investigated HDAC10-specific inhibitors. Therefore, it is important to study the biological functions of HDAC10 for the future development of specific HDAC10 inhibitors. In this review, we analyzed the biological functions, mechanisms and inhibitors of HDAC10, which makes HDAC10 an appealing therapeutic target.

Introduction

Nuclear DNA in eukaryotic cells always combines with histones before packaging into the chromatin. However, a fundamental question is how the chromatin is regulated when and where it is necessary. The existing evidence presented that ATP-dependent chromatin remodeling as well as covalent chromatin modification may contribute to this regulation [1]. Covalent chromatin modification includes acetylation, phosphorylation, methylation, ubiquitination and ADP-ribosylation [2,3]. Acetylation, as the first discovered modification, is the most studied and best characterized among all modifications. There is compelling evidence that acetylation of lysine residues at amino acid termini greatly affects transcriptional regulations [2].

Histone deacetylases (HDACs) serve as an ‘eraser’, which remove acetate from acetylated histone as well as other non-histone proteins [4,5]. Generally, HDACs are also known as lysine acetyltransferases as well as lysine deacetylases [6]. Additionally, HDACs exert effects on post-translational modifications, such as ubiquitination and methylation, and can influence gene transcription by increasing the interaction between DNA and histone [7–9]. In eukaryotic cells, HDACs may come from prokaryotic enzymes, similar to acetylpolyamine amidohydrolases [7,10]. Currently, HDACs are divided into four classes [11]. In 2002, Fischer et al. [12], Tong et al. [5], Kao et al. [13] and Guardiola and Yao [14] reported a novel enzyme that shares functional characterizations with other class II members, and named it HDAC10.

In this review, we focus our attention on the progress of studies on the role of HDAC10 in various tumors and non-tumor diseases. Particular emphasis is given to its functions and mechanisms.

Structures and catalytic mechanisms of different HDACs

Structures of class II HDACs

Class II HDACs are subclassified as IIa and IIb. Class IIa HDACs (HDAC4, 5, 7, 9) are defined by a functionally essential N-terminal domain, which can regulate nuclear–cytoplasmic shuttling as well as specific DNA-binding. The cellular trafficking of class IIa HDACs is determined by intrinsic nuclear import or export signals as well as specific binding sites for 14-3-3 proteins [15]. Through binding with the 14-3-3 proteins, Class IIa HDACs can stimulate cytoplasmatic retention and nuclear export in a phosphorylation-dependent manner. These processes in turn affect the activity of transcription factors, such as myocyte enhancing factor-2 [16,17].

Class IIb HDACs include HDAC6 and HDAC10. HDAC6 contains two tandem deacetylase domains and a C-terminal zinc finger [18]. HDAC10 is structurally related to HDAC6. The HDAC10 gene localizes to chromosome 22 [14]. Consisting of 20 exons, HDAC10 contains two spliced transcripts [5,12] and also contains N-terminal catalytic domain and C-terminal leucine-rich domain. Specifically, the N-terminal catalytic domain of HDAC10 is similar to the deacetylase domain of other known class II HDACs, but the C-terminal catalytic domain does not contain residues that are necessary for enzymatic functions. The existence of both domains may confer resistance to trapoxin B and sodium butyrate [5,14]. HDAC10 is member of the arginase/deacetylase superfamily and is expressed differentially in the cytoplasm and nucleus [10,12]. It may also repress transcription except for the deacetylation activity in the nucleus [14]. Moreover, HDAC10 expressed in most human tissues, including the kidney, pancreas, liver, spleen, heart, testis, brain and placenta [5]. Emerging evidence has established that HDAC10 is responsible for the regulation of polyamine. Using X-ray crystallography, researchers have observed that HDAC10 has a unique conserved glutamate gatekeeper that may promote N8-acetylspermidine hydrolysis, serving as a polyamine deacetylase (PDAC) [6,19].

Noticeably, class II HDACs show 23–81% amino acid similarity with conserved deacetylase domains. Moreover, they all have cytoplasmic localization, which implies that class II HDACs play significant role in cytoplasmic functions [13,20,21].

Catalytic mechanisms of HDACs

Class I, II and IV HDACs require zinc ion to exert enzyme activity. The X-ray crystallography has determined catalytic domain structures of Class I, II and IV HDACs, which contain open α/β-family of folds and stranded parallel β-sheets [22]. These structures make contributions to the binding of HDACs active sites and HDAC inhibitors (HDACIs). A model of action proposed by Wu et al. [23] suggested that H143, a histidine residue, could function as a base to accept protons from zinc-bound molecules in a rate-determining step. Then the accepted proton will be shuttled to the amide nitrogen atom to facilitate the cleavage of amide bond [24].

The class III HDACs has a common model of action that requires cofactor NAD+ [25]. A structural study found that the catalytic domain of class III HDACs locates in a cleft, which could constitute a protein tunnel where the substrate could combine with NAD+. Mechanically, based on the catalytic structure of class III HDACs, cleavable nicotinamide from NAD+ and ADP-ribose could transfer to acetylated lysine [26].

Biological characterization and mechanism of HDAC10 in tumors

In 2000 and 2011, Hanahan and Weinberg proposed six and additional four hallmarks of tumors, respectively [27,28]. These conceptions promoted the understanding of the diversity of tumors. Here, we focus mostly on HDACs that affect the biology of tumors and tumorigenesis, and summarize the mechanistic underpinnings concerning cell proliferation, cell apoptosis, cell invasion, migration, metastasis, angiogenesis and other tumor-related biological functions (Figure 1 and Table 1).
Figure 1
HDAC10 regulate cell proliferation, cell apoptosis, cell metastasis and angiogenesis in cancer cells

(A) Roles of HDAC10 in cell proliferation. (B) Roles of HDAC10 in cell apoptosis. (C) Roles of HDAC10 in cell metastasis. (D) Roles of HDAC10 in angiogenesis.

Figure 1
HDAC10 regulate cell proliferation, cell apoptosis, cell metastasis and angiogenesis in cancer cells

(A) Roles of HDAC10 in cell proliferation. (B) Roles of HDAC10 in cell apoptosis. (C) Roles of HDAC10 in cell metastasis. (D) Roles of HDAC10 in angiogenesis.

Table 1
Overview of biological roles of HDAC10 in several malignant tumors
TumorExpression levelFunctionTarget/Signaling pathwayCell line/TissueReference
NSCLC Elevated Cell proliferation, Cell apoptosis AKT, BCL2, BAK A549, H358 and H460 cell [18
Lung adenocarcinoma Elevated Cell proliferation, cancer stemness, Tumor immune TGF-β pathway, SOX9, CD44, SLUG HDAC10 KO mice, HDAC10 WT mice [19
Lung cancer Elevated Cell proliferation LKB1–AMPK signaling, G6PD, ROS H1299, H157, H1944, H460 and A549 cell [23
Lung cancer Elevated Cell proliferation, Cell cycle H3, HMGA2 H1299, H441, H23, H157, H2122, H358, A549, PC9, H1975, H322, H292, H460, H522, H661 and ADLC-5M2 cell [25
Lung cancer Decreased Cell metastasis Cx43, FSTL1, H3, H4, S100A10, MMP-2, LAMA4, MTSS1 PG cell [41
RCC Decreased Cell proliferation, cell invasion β-catenin ACHN, Caki-2 cell, 45 primary RCC tissues and adjacent normal tissues [20
Gastric cancer Cell apoptosis Caspase-3, Caspase-9, Bid, TXNIP, ROS SNU-620 cell [35
Gastric cancer Angiogenesis Hsp70, VEGFR1, VEGFR2 SNU620 cell [51
Colorectal cancer Cell apoptosis Wnt pathway, TCF7L2 SW480, HCT116 cell [32
Colon cancer Angiogenesis Hsp70, VEGFR1, VEGFR2 HCT116 cell [51
Colon cancer Elevated Mismatch repair MSH2, MLH1, MSH6 100 colon cancer tissues [81
Cervical cancer Cell metastasis MMP-2, MMP-9 HeLa-S3 cell, 60 cancer tissue and normal tissue [42
Cervical cancer Autophagy LAMP2A-positive lysosome HeLa cell [75
Cervical cancer Mismatch repair MSH2 HeLa cell [80
Cervical cancer and Osteosarcoma Drug resistance hSSB1, p300 HeLa and U2OS cells [62
HCC Cell metastasis H3K9/14, C/EBPα, miR-223, integrin αV subunit SMMC-7721 cell [43
HCC HBV-infected HCC Promoter polymorphism 1095 HBV infection patient tissues [82
Neuroblastoma Drug resistance Lysosomal exocytosis, DNA damage SK-N-BE (2)-C, IMR-32 and SK-N-AS cell [55
Neuroblastoma Drug resistance Hsp70, Hsc70 BE [2]-C, Kelly and IMR32 cell [57,58
Ovarian Decreased Drug resistance DNA repair UWB1.289 cell [59
Prostate cancer Drug resistance AR-V7, flAR, BRD4, NCOR2, DUB3, BRD4 C4-2, PC-3, 22Rv1, DU145, LNCaP, VCaP and LAPC4 cells [66,67
Adrenocortical cancer Chromatin modulator Methylation 44 adrenocortical cancer and 6 normal tissues [83
Melanoma Decreased Gene expression HDAC Melanoma tissue and normal samples [84
TumorExpression levelFunctionTarget/Signaling pathwayCell line/TissueReference
NSCLC Elevated Cell proliferation, Cell apoptosis AKT, BCL2, BAK A549, H358 and H460 cell [18
Lung adenocarcinoma Elevated Cell proliferation, cancer stemness, Tumor immune TGF-β pathway, SOX9, CD44, SLUG HDAC10 KO mice, HDAC10 WT mice [19
Lung cancer Elevated Cell proliferation LKB1–AMPK signaling, G6PD, ROS H1299, H157, H1944, H460 and A549 cell [23
Lung cancer Elevated Cell proliferation, Cell cycle H3, HMGA2 H1299, H441, H23, H157, H2122, H358, A549, PC9, H1975, H322, H292, H460, H522, H661 and ADLC-5M2 cell [25
Lung cancer Decreased Cell metastasis Cx43, FSTL1, H3, H4, S100A10, MMP-2, LAMA4, MTSS1 PG cell [41
RCC Decreased Cell proliferation, cell invasion β-catenin ACHN, Caki-2 cell, 45 primary RCC tissues and adjacent normal tissues [20
Gastric cancer Cell apoptosis Caspase-3, Caspase-9, Bid, TXNIP, ROS SNU-620 cell [35
Gastric cancer Angiogenesis Hsp70, VEGFR1, VEGFR2 SNU620 cell [51
Colorectal cancer Cell apoptosis Wnt pathway, TCF7L2 SW480, HCT116 cell [32
Colon cancer Angiogenesis Hsp70, VEGFR1, VEGFR2 HCT116 cell [51
Colon cancer Elevated Mismatch repair MSH2, MLH1, MSH6 100 colon cancer tissues [81
Cervical cancer Cell metastasis MMP-2, MMP-9 HeLa-S3 cell, 60 cancer tissue and normal tissue [42
Cervical cancer Autophagy LAMP2A-positive lysosome HeLa cell [75
Cervical cancer Mismatch repair MSH2 HeLa cell [80
Cervical cancer and Osteosarcoma Drug resistance hSSB1, p300 HeLa and U2OS cells [62
HCC Cell metastasis H3K9/14, C/EBPα, miR-223, integrin αV subunit SMMC-7721 cell [43
HCC HBV-infected HCC Promoter polymorphism 1095 HBV infection patient tissues [82
Neuroblastoma Drug resistance Lysosomal exocytosis, DNA damage SK-N-BE (2)-C, IMR-32 and SK-N-AS cell [55
Neuroblastoma Drug resistance Hsp70, Hsc70 BE [2]-C, Kelly and IMR32 cell [57,58
Ovarian Decreased Drug resistance DNA repair UWB1.289 cell [59
Prostate cancer Drug resistance AR-V7, flAR, BRD4, NCOR2, DUB3, BRD4 C4-2, PC-3, 22Rv1, DU145, LNCaP, VCaP and LAPC4 cells [66,67
Adrenocortical cancer Chromatin modulator Methylation 44 adrenocortical cancer and 6 normal tissues [83
Melanoma Decreased Gene expression HDAC Melanoma tissue and normal samples [84

Abbreviations: AKT, protein kinase B; AMPK, AMP-activated protein kinase; AR-V7, androgen receptor-V7; BAK, BCL2 antagonist/killer; BCL2, B-cell lymphoma-2; Bid, BH3 interacting domain death agonist; BRD4, bromodomain-containing protein 4; Cx43, connexin 43; C/EBPα, CCAAT enhancer-binding protein; DUB3, ubiquitin-specific peptidase 17 like family member 2; flAR, full length androgen receptor; FSTL1, follistatin-like 1; G6PD, glucose-6-phosphate dehydrogenase; HBV, hepatitis B virus; HCC, hepatic cell carcinoma; HMGA2, high mobility group A 2; Hsp70, heat shock protein 70; hSSB1, human single-stranded DNA binding protein; LAMA4, laminin subunit α 4; LAMP2A, lysosomal associated protein 2 A; LKB1, liver kinase B1; MLH1, mutL homolog 1; MMP-2, matrix metalloproteinase-2; MMP-9, matrix metalloproteinase-9; MSH2, mutS homolog 2; MSH6, mutS homolog 6; MTSS1, MTSS I-BAR domain containing 1; NCOR2, nuclear receptor co-repressor 2; NSCLC, non-small-cell lung cancer; RCC, renal cell carcinoma; ROS, reactive oxygen species; SOX9, sex-determining region Y box protein 9; TCF7L2, transcription factor 7 like 2; TGF-β, transforming growth factor-β; TXNIP, thioredoxin interacting protein; VEGFR1, vascular endothelial growth factor receptor 1; VEGFR2, vascular endothelial growth factor receptor 2.

HDAC10 and cell proliferation

HDAC10 plays an essential role in the regulation of cancer cell growth. It has been demonstrated that it can prompt cell proliferation in non-small-cell lung cancer (NSCLC) [29]. In contrast, HDAC10 suppresses cancer cell growth in other malignant tumors, including lung adenocarcinoma [30] and renal cell carcinoma (RCC) [31]. Akt is a key molecule in the PI3K-AKT pathway, and is involved in cell proliferation, survival and other key functions [32]. Analogously, HDAC10 overexpression significantly facilitates NSCLC cell growth by regulating the Ser473 phosphorylation of AKT [29]. In lung adenocarcinoma, deletion of HDAC10 accelerates the progression of KRAS-driven cancer both in vivo and in vitro. Specifically, by activating the transforming growth-factor β (TGF-β) pathway, deletion of HDAC10 promotes the expression of sex-determining region Y box protein 9 (SOX9), which subsequently up-regulates the expression of SLUG, as well as CD44. These processes contributes to the growth of lung cancer spheres via SOX9-mediated stem-like properties, suggesting that HDAC10-TGF-β-SOX9-SLUG/CD44 axis plays an essential role in lung adenocarcinoma [30].

AMP-activated protein kinase (AMPK) regulates biological functions in tumors that are mediated by liver kinase B1 (LKB1), such as cell survival and transcription, via the mTOR pathway [33]. Induced by LKB1–AMPK signaling, phosphorylated HDAC10 is transported from the the nucleus to the cytoplasm and further enhances the expression of glucose-6-phosphate dehydrogenase (G6PD). This decreases the level of reactive oxygen species (ROS) and promotes lung cancer cell proliferation [34]. The cases described above suggest that the LKB1–AMPK-HDAC10-G6PD-ROS pathway might be important to tumor cell proliferation. However, in RCC cells, suppressed expression of HDAC10 significantly promotes the phosphorylation of β-catenin and thus plays a part in anti-proliferation [31] (Figure 1A).

Perturbed cell cycle is also a growth-regulation way in cancer cell [35]. Previous studies have shown that by inhibiting histone H3 deacetylation around the let-7f-2/miR-98 promoter, HDAC10 suppresses HMGA2 expression which target to cyclin A2 promoter, and further inhibits the transcription of cyclin A2 [30,36]. The signaling pathways: HDAC10-let-7f-2/miR-98-HMGA2-cyclin A2 arrests the G2/M transition and finally inhibits lung cancer cell proliferation. Evidence suggests that both cell cycle inhibitors (such as P21 and P27) and promoters (such as cyclins E1 and D1) play a vital role in cancer progression [37–39]. HDAC10 plays an oncogenic role by inhibiting the expression of P27, P21 and enhancing that of cyclins D1 and E1 [29] (Figure 1A).

HDAC10 and cell apoptosis

Cancer cells will not die in a scenario that too little apoptosis happens [40]. Numbers of proteins and signaling are involved in cell apoptosis. It has been established that overexpressed anti-apoptotic proteins (such as those in the Bcl-2 family) as well as down-regulated proteins (such as Bid, BIK and BAK) may disrupt the balance between apoptosis and anti-apoptosis [41,42]. By targeting AKT, HDAC10 affects the expression of B-cell lymphoma-2 (BCL2) as well as BCL2 antagonist/killer (BAK), which induces apoptosis in lung carcinoma [29]. In colorectal cancer, inhibited HDAC10 expression promotes cell apoptosis by depleting transcription factor 7 like 2 (TCF7L2), which attenuates the Wnt pathway [43]. ROS, generated from mitochondrial damage or oxidative stressors, may promote caspases and induce apoptosis [44,45]. Lee et al. found that a low level of HDAC10 in gastric cancer may activate proapoptotic molecules including caspase-3, caspase-9, and Bid through the thioredoxin interacting protein (TXNIP)-induced ROS signaling pathway [46] (Figure 1B). Although previous studies have determined limited mechanisms in lung, colorectal and gastric tumors, including the HDAC10-AKT-BCL2-BAK pathway, the HDAC10-TCF7L2-Wnt pathway and the HDAC10-TXNIP-ROS-caspase-3/caspase-9/Bid pathway, it is not yet clear whether these mechanisms exist in other tumors [29,43,46]. Therefore, advances in research on the mechanisms of HDAC10 will be key to unraveling its potential importance in tumors.

HDAC10 and cell metastasis

Tumor cell metastasis is a multistep process including cell adhesion, invasion, migration and dissemination at distant organs [47,48]. Invasion- and migration-related molecules, such as matrix metalloproteinases (MMPs), and S100A10 are dysregulated in various cancer cell lines [49–51]. Zhao et al. [52] reported that HDAC10 shows low expression levels in pulmonary giant cell carcinoma cells and is subject to regulation by connexin 43 (Cx43). As Cx43 is overexpressed, the expression of follistatin-like 1 (FSTL1) is elevated, via the enhanced binding between HDAC10-mediated acetylation of H3 and H4 and the promoter of FSTL1. The Cx43-HDAC10-FSTL1 axis not only contributes to the low expression levels of S100A10, MMP-2 and laminin subunit α 4 (LAMA4), but also enhances the expression of MTSS I-BAR domain containing 1 (MTSS1), which plays a pivotal role in the suppression of both invasion and metastasis [52]. In metastatic cervical squamous cancer cells, HDAC10 serves a tumor suppressor role through the regulation of MMPs. Mechanistically, due to the combination of HDAC10 and the promoters of MMP-2 (especially the AP1-binding site) and MMP-9 (especially the NF-κB- and sp1-binding sites) the decreased level of histone acetylation impedes the binding function of polymerase II, weakens the expression levels of MMP-2 and MMP-9 and restrains cancer cell invasion and migration [53]. HDAC10 also deacetylates acetyl-H3K9/14 and acetyl-C/EBPα, preventing their recruitment to the promoter of miR-223 in sulfatide-treated hepatocellular cancer (HCC) cells. The low expression of miR-223 further facilitates the expression of integrin αV subunit and then attenuates HCC cell migration as well as metastasis [54]. The β-catenin pathway is altered in various tumors and also plays important roles in carcinogenesis [55,56]. In renal cell carcinoma (RCC), overexpressed HDAC10 restrains RCC cell invasion by inhibiting phosphorylated nuclear β-catenin expression [31] (Figure 1C). Although these studies are interesting, they were mainly based on overexpression experiments. Therefore, the mechanism of HDAC10 in tumor metastasis must be characterized in more detail.

HDAC10 and angiogenesis

Angiogenesis is an indispensable process in the early stage of tumor growth [57]. Angiogenesis involves several pro-angiogenic proteins, including vascular endothelial growth factor (VEGF), TGF-β, extracellular regulated protein kinases (ERKs) and others [58–60]. Duan et al. [61] reported that overexpressed HDAC10 deacetylates H3 and H4 in promoter of phosphatase and tensin homolog 22 (PTEN22) and consequently inhibits polymerase II from binding to PTEN22 promoter. The suppressed expression of PTEN22 subsequently increases ERK1/2 activation and ultimately facilitates the formation of tubes in vivo and in vitro. Because of this, it was speculated that the HDAC10-PTEN22-ERK1/2 signaling pathway may contribute to tumor angiogenesis. HDAC10 also regulates angiogenesis via depletion of VEGFR in gastric and colon cancer cells. Mechanistically, HDAC10 obstructs heat shock protein (Hsp) 90 bound to VEGF receptor 1 (VEGFR1)/VEGFR2, but promotes the combination between Hsp70 and VEGFR1/VEGFR2 [62]. This imbalanced binding leads to proteasomal-dependent degradation of VEGFRs, which may regulate angiogenesis (Figure 1D).

HDAC10 and drug resistance

Drug resistance is a common phenomenon during chemotherapy. It not only limits the therapeutic effect but can even lead to treatment failure [63]. The altered drug metabolism, mutated drug targets and elevated drug efflux rate contribute to drug resistance [64,65]. Down-regulation of HDAC10 may restore the sensitivity of doxorubicin in neuroblastoma. Ridinger et al. [66] reported that suppressing HDAC10 expression promotes intracellular accumulation of doxorubicin by inhibiting lysosomal exocytosis, which results in cell death with enhanced double-strand breaks (DSBs) as well as DNA damage. Additionally, autophagy, activated via therapeutic stress, participates in drug resistance and multidrug resistance (MDR) [67]. Consistent with this point, Oehme et al. [68,69] found that HDAC10 deletion acetylated Hsp70/heat shock cognate 70 (Hsc70), and impairs the autophagic flux by thwarting the blend between autophagosomes and lysosomes, which allows drug-resistant neuroblastoma cell to recover sensitivity to doxorubicin. A study that combined bioinformatics analyses and cell experiments found that low HDAC10 expression both intensifies the cytotoxicity of ovarian cancer cells to cisplatin and constrains DNA repair [70].

Many cytotoxic events can break DNA double strands and result in cell death [71]. Encountering DNA damage, various proteins, such as human single-stranded DNA binding protein 1 (hSSB1), will repair the flawed sites [72]. Wu et al. [73] found that p300 acetylates hSSB1 Lys94 when it localizes to impaired sites, and recovers DNA stability. However, up-regulated HDAC10 reverses this process and makes tumor cells more responsive to chemotherapy. Castration-resistant prostate cancer (CRPC), arising from resistance to androgen deprivation therapy (ADT), is a tricky problem [74]. Previous studies have reported that bromodomain and extra-terminal protein inhibitor (BETi) can deteriorate the androgen receptor (AR) signaling pathway. Moreover, in prostate cancer cells, elevated expression of bromodomain-containing protein 4 (BRD4, a member of BET family), induced by BETi, confers resistance to these inhibitors [75,76]. Jin et al. [77] found that low expressed nuclear receptor co-repressor 2 (NCOR2)–HDAC10 complex is negatively associated with deubiquitinase ubiquitin-specific peptidase 17 like family member 2 (DUB3), which may interact with BRD4 and further inhibit sensitivity to BETi in prostate cancer cells and in vitro. Although the roles of HDAC10 in drug resistance have not been explored completely, experiments suggest that the NCOR2-HDAC10-DUB3-BRD4 signaling pathway might be useful as a regulator of drug resistance in tumors [77]. AR is a significant target in treating CRPC, and silencing HDAC10 also reduces the transcriptional activity of AR-V7 and full-length AR (flAR) in prostate cells [78], which implies that HDAC10 has potential therapeutic value.

Other biological functions

Cancer stem cells (CSCs) are cells hidden in tumors that are capable of promoting tumor growth, progression and resistance treatments [79,80]. Many molecules, such as SOX9, SLUG and CD44, may help determine stem cell state [81,82]. In lung adenocarcinoma, SOX9, SLUG and CD44 are activated by the down-regulation of HDAC10 and stimulation of TGF-β, which mediates CSC-related cancer progression [30]. HDAC10 impacts immune and inflammation function as well. HDAC10-deleted Foxp3+ Treg cells have immunosuppressive functions and may play roles in alleviating immune-related colitis and prolonging cardiac allograft survival in MHC-mismatched mice [83]. HDAC10 deletion also recruits massive macrophages (especially M2 macrophages) into the lung cancer microenvironment. Considering that M2 macrophages may secrete anti-inflammatory molecules and promote tumor activity, HDAC10 may accelerate tumor progression by increasing tumor inflammation [30,84]. An additional effect of deletion of HDAC10 is chaperone-mediated autophagy (CMA), a form of autophagy that occurs via selective cytosolic protein transfer [85]. In knockout HDAC10 cervical cancer cells, Obayashi et al. [86] identified that increased expression levels of lysosomal associated protein 2 A (LAMP2A) and increased accumulation of LAMP2A-positive lysosomes near the nucleus raised, which may be a sign of activated CMA [87,88]. This characteristic may be effective for cancer treatment.

The mismatch repair system (MMR) is important in correcting flaws occurring during the stage of DNA replication [89]. It has been shown that mutL homolog 1 (MLH1), mutS homolog 2 (MSH2) and MSH6 commonly participated in MMR [90]. HDAC10 can trigger MSH2 activity initiated by MSH2 deacetylation at Lys73 in HeLa cells, following improved MMR activation [91]. A study that compared colon cancer cells and adjacent cells also revealed that low HDAC expression level in normal cells were negatively correlated with MSH2, MLH1 and MSH6 [92]. This may account for the different prognoses between normal and tumor cells.

HDAC10 can perform regulatory roles through other epigenetic modifications, i.e. transcription regulation, methylation and promoter polymorphism [93–95]. In adrenocortical cancer cells and adenoma cells, HDAC10 is significantly methylated and its expression level dramatically decreases with hypermethylation [94]. Uzdensky et al. [95] observed down-regulated HDAC10 during transcription deregulation of melanoma progression. HDAC10 also participates in influencing the occurrence and onset age of HBV infection in HCC patients due to the promoter polymorphism, notably HDAC10-589C>T. The ‘T’ allele in HDAC10-589C>T enhances transcription activity, and might spur HCC progression by increasing HDAC10 expression [93]. Other study identified that frameshift deletions, one type of repeated alterations, occurred in HDAC10 among anaplastic thyroid cancer specimen [96]. According to Lourdusamy et al. [97], a large number of genes, including BRD1, HIRA and HDAC10 are expressed at low levels in spinal ependymoma. However, the detailed mechanisms underlying the activity of HDAC10 in spinal ependymoma still need to be elucidated. These studies may manifest an alternate form of tumor regulation (Figure 2A). It is worth noting that the specific mechanisms of the involvement of HDAC10 in other functions also remain unresolved, and further studies are needed. Nonetheless, the studies reviewed herein demonstrate the promise of HDAC10 as a molecular target for cancer.

Role of HDAC10 in non-tumor diseases and its clinical applications

Figure 2
Role of HDAC10 in non-tumor diseases and its clinical applications

(A) Role of HDAC10 in non-tumor diseases. (B) Clinical applications of HDAC10.

Figure 2
Role of HDAC10 in non-tumor diseases and its clinical applications

(A) Role of HDAC10 in non-tumor diseases. (B) Clinical applications of HDAC10.

Prognostic roles of HDAC10

The potential prognostic roles of HDAC10 have been explored. Up-regulated HDAC10 is associated with favorable overall survival (OS) in colon cancer, gastric cancer, RCC and NSCLC patients [31,92,98,99]. However, it should be noted that Liu et al. [100] studied the OS data of 180 NSCLC patients and found that up-regulated HDAC10 predicted poor OS. Moreover, HDAC10 is also an independent predictor of treatment-free survival (TFS) as well. HDAC10 level is associated with poor TFS in chronic lymphocytic leukemia (CLL) [101]. In this disease, high expression levels of HDAC are indirectly associated with a poor prognosis [102–104]. PD-L1 is expressed in various cancers and its clinical therapeutic value has been validated [105]. Due to enhanced PD-L1 expression in NSCLC patients with high HDAC10 expression, HDAC10 could function as a biomarker for the evaluation of PD-L1 treatment [100]. The elevated radiosensitization caused by inhibiting HDAC10 involves down-regulation of Rad51a, a component of DNA repair pathways [106]. In addition, positive HDAC10 expression is correlated with adverse clinical features, such as larger tumor size, poor tumor stage and more lymph node metastasis [99] (Figure 2B).

HDAC10 in other non-tumor diseases and its pathophysiological functions

Respiratory system diseases

An important role of HDAC10 has been found in asthma-induced eosinophilic airway inflammation. Zhang et al. [107] demonstrated that glucocorticoid (GC) and anacardic acid (AA) have the ability to alleviate IL-4, IL-5 and IL-13 and ameliorate airway inflammation invivo, which depends on the low histone acetylation induced by elevated HDAC10 in memory T cells. A study that examined titanium dioxide (TiO2), a latent occupational carcinogen [108] in lung cells, reported that TiO2 particles provoked ROS (especially superoxide) and HDAC10 expression after lung cell are treated at 100 and 160 μg/cm2 for 24 h, respectively [109]. This implies that heritable epigenetic changes may serve as a reply to TiO2 particle exposure. Moreover, HDAC10 is also a potential pathogenic gene in emphysema [110].

Urinary system diseases

HDAC10 is also a latent biomarker in immunoglobulin A nephropathy (IgAN) and renal fibrosis as well [111,112]. HDAC10 protein levels are significantly higher in fibrotic kidneys. However, piceatannol treatment does not diminish HDAC10 expression but the results hint that HDAC10 may regulate renal fibrosis via other signaling pathways [111]. To determine a biomarker for IgAN, Guo et al. [112] utilized samples from the Gene Expression Omnibus (GEO) database and found that HDAC10 existed in monocytes of IgAN samples, which enriches in both alcoholism and chromatin modifying enzymes via construction of functional interaction (FI) network.

Nervous system diseases

HDAC10 is associated with many nervous system diseases. Kebir et al. [113] indicated that one single nucleotide polymorphism (SNP) (rs7634112) located in HDAC10 is significantly associated with schizophrenia. They devised a model that incorporates HDAC10, HDAC3 and HDAC9 to divide schizophrenia patients with high accuracy. A Korean study confirmed these results and selected a new SNP (rs1555048) for the Korean population [114]. Wang et al. [115] reported that decreased HDAC10 expression may aggravate post-intracerebral hemorrhage inflammation by elevating downstream PTPN22 and activating NLRP3 inflammasomes in rats. HDAC10 can modulate drug addiction as well. González et al. [116] reported that single-dose methamphetamine (METH) enhances HDAC10 expression in the medial prefrontal cortex of rat and that such up-regulation influences H4ac enrichment, which may account for the modified cognitive functions observed after using psychostimulants. The translocation of Olig1 protein involves brain development as well as multiple sclerosis [117,118]. In oligodendrocytes, HDAC10 represses Olig1 Lys150 acetylation, which leads to Olig1 protein being retained in cytoplasm [119]. In mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), HDAC10 mRNA is significantly up-regulated. Meanwhile, increased HDAC10 expression has also been found in cytoplasm instead of the nucleus [120]. This subcellular distribution hints at potential role of HDAC10 in regulating MTLE-HS pathophysiology.

Hormone regulation

Many studies have opened new doors into the potential functions of HDAC10 in hormone regulation. Xu et al. [121] found that the alteration of decreased luteinizing hormone (LH) surge stimulated by estradiol (E2) in middle age female rats may mediated by HDAC10. Specifically, in the anterior hypothalamus, the attenuated HDAC10 expression and enhanced H3 acetylation induced by E2 were not observed in middle-aged female rats. A study from China illustrated the important role of HDAC10 in melanogenesis [122]. HDAC10 restores melanogenesis by deacetylating paired box protein 3 (Pax3) and KRAB-associated protein 1 (KAP1), which relieves the repressed promoters of microphthalmia-associated transcription factor (MITF) as well as tyrosinase-related protein 1 (TRP-1) and TRP-2 in melanoma cells [122]. These processes ultimately prove that melanogenesis is mainly achieved through HDAC10/Pax3/KAP1 pathway.

Lipid metabolism

The role of HDAC10 in regulating lipid metabolism has also been investigated. Qian et al. [123] found that HDAC10 expression decreases in obese humans and other animals (including mice and monkeys). In one study, the level of HDAC10 was markedly reduced in the medial hypothalamus of fasting mice, but researchers did not investigate its impact on AcH3 and AcH4 expression [124]. A study of benzyl butyl phthalate (BBP) found that it reduces HDACs (including HDAC10) and further contributes to acetylation of H3K9, which drives adipogenesis in mesenchymal stem cells (MSCs) [125].

Human immunodeficiency virus infection

The pathogenetic mechanisms of human immunodeficiency virus (HIV) are still being explored, which is crucial to develop blockbuster drugs [126]. Recent research suggests that HDAC10 takes part in HIV infectivity and thus can be used for its treatment [127–129]. Ran et al. identified that a virus-associated envelope glycoprotein (vEnv), one type of defective viral particle, mediates histone deacetylation via down-regulation of HDAC10 in Jurkat T cell, which ultimately elevates the infectivity of the virus and leads to HIV infection [127]. In CD4+ T cells, down-regulating HDAC10 expression promotes HIV-1 replication by increasing its interaction with DNA. Meanwhile, HDAC10 also combines with HIV-1 integrase (IN), lessening its reciprocal action with cellular protein lens epithelium-derived growth factor (LEDGF/p75), and ultimately deteriorating HIV-1 integration, which makes HDAC10 an inhibitor of HIV-1 replication [128]. Currently, antiretroviral drugs can prolong the life expectancy of HIV patients since it was introducted [130]. Rodriguez et al. reported that both raltegravir alone and in combination with morphine facilitate the level of HDAC10 [129]. However, further investigation is necessary to illustrate the underlying therapeutic mechanism.

Other diseases

HDAC10 orchestrates various biological functions. Pinto et al. [131] found that HDAC10 may mediate nutrition-associated growth. After restricting food in vivo or starving serum in vitro, HDAC10 expression apparently increased which is induced by inhibiting mTOR, and elevated levels of HDAC10 activated autophagy via Hsp70 deacetylation, thereby repressing cell viability [131]. HDAC10 also affects inflammation in the temporomandibular joint. Down-regulated HDAC10 suppresses the IL-1β/NF-κB pathway and its related inflammatory response invitro [132]. In addition, in embryonic as well as induced pluripotent stem cells, HDAC10 enhances the level of chromatin remodelers [133]. In retinal ganglion cells, excitotoxicity alters HDAC10 localization to the cytoplasm [134]. In patients with vasospastic angina, apparently DNA gain was observed in HDAC10 [135]. However, it remains to be explored the detailed HDAC10-related mechanism or therapeutic value (Table 2).

Table 2
Overview of selected biological roles of HDAC10 in non-tumor diseases
DiseaseExpression levelFunctionsTargets/Signaling pathwaysCell lines/Tissues/Animal modelReference
Eosinophilic airway inflammation Elevated Inhibit airway inflammation IL-4, IL-5, IL-13 CD4+ CD45RBlow cell [96
TiO2-associated lung disease Elevated Cellular response Reactive oxygen species A549 cell [97
Emphysema Pathogenic gene Copy number gains 32 emphysema blood samples [99
IgAN Chromatin modifying enzymes 8 IgAN blood samples and 9 normal blood samples [101
Renal fibrosis Elevated Regulate renal fibrosis C57BL/6 male mice [100
Schizophrenia Diagnostic value 278 Korean schizophrenia patients, 626 Caucasian schizophrenia parents [102,103
Post-ICH inflammation Decreased Aggravate inflammation response PTPN22/NLRP3 6 ICH samples and S-D rat [104
Drug addiction Elevated Affect cognitive function H4ac enrichment C57BL/6 mice [105
Multiple sclerosis Decreased Affect oligodendrocytes Oligo1 lysine 150 acetylation Mouse neural progenitor cells, HEK293T cell [108
MTLE-HS Elevated Transcription regulation 28 MTLE-HS samples [109
LH secretion Decreased Reduce LH secretion H3 acetylation S-D rat [110
Melanogenesis Promote melanogenesis Pax3/KAP1 HEK293 cell and B16F10 cell [111
Adipogenesis Decreased Promote adipogenesis H3K9 acetylation MSCs [114
HIV infection Decreased Promote HIV infection IN/LEDGF/p75, histone deacetylation CD4+ T cell [116,117
Nutrition-associated growth Elevated Inhibit cell viability mTOR, Hsp70, autophagy S-D rat, Huh7 cell [120
TMJ inflammation Decreased Inhibit inflammatory response IL-1β/NF-κB 13 TMJ samples [121
DiseaseExpression levelFunctionsTargets/Signaling pathwaysCell lines/Tissues/Animal modelReference
Eosinophilic airway inflammation Elevated Inhibit airway inflammation IL-4, IL-5, IL-13 CD4+ CD45RBlow cell [96
TiO2-associated lung disease Elevated Cellular response Reactive oxygen species A549 cell [97
Emphysema Pathogenic gene Copy number gains 32 emphysema blood samples [99
IgAN Chromatin modifying enzymes 8 IgAN blood samples and 9 normal blood samples [101
Renal fibrosis Elevated Regulate renal fibrosis C57BL/6 male mice [100
Schizophrenia Diagnostic value 278 Korean schizophrenia patients, 626 Caucasian schizophrenia parents [102,103
Post-ICH inflammation Decreased Aggravate inflammation response PTPN22/NLRP3 6 ICH samples and S-D rat [104
Drug addiction Elevated Affect cognitive function H4ac enrichment C57BL/6 mice [105
Multiple sclerosis Decreased Affect oligodendrocytes Oligo1 lysine 150 acetylation Mouse neural progenitor cells, HEK293T cell [108
MTLE-HS Elevated Transcription regulation 28 MTLE-HS samples [109
LH secretion Decreased Reduce LH secretion H3 acetylation S-D rat [110
Melanogenesis Promote melanogenesis Pax3/KAP1 HEK293 cell and B16F10 cell [111
Adipogenesis Decreased Promote adipogenesis H3K9 acetylation MSCs [114
HIV infection Decreased Promote HIV infection IN/LEDGF/p75, histone deacetylation CD4+ T cell [116,117
Nutrition-associated growth Elevated Inhibit cell viability mTOR, Hsp70, autophagy S-D rat, Huh7 cell [120
TMJ inflammation Decreased Inhibit inflammatory response IL-1β/NF-κB 13 TMJ samples [121

Abbreviations: ICH, intracerebral hemorrhage; IL, interleukin; IN, HIV-1 integrase; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor κB; NLRP3, NOD-like receptors 3; PTPN22, protein tyrosine phosphatase nonreceptor type 22; TMJ, temporomandibular joint.

HDAC10 inhibitors

After constructing the homology model structure of HDAC10, Uba et al. further validated its reliability [136,137]. A group, focused on the tunnel behavior of HDAC10, suggested that the amino acids in tunnel-like sites of HDAC10 are subtly different from other HDACs (such as HDAC8 and HDAC11) identified a non-conserved amino acid in the wall of these sites [138]. Researchers have also found that HDAC10 contains Zn2+-binding groups and has additional interactions with inhibitors when accommodating with them [139]. Moreover, the X-ray crystal structure of zebrafish HDAC10 indicates that the gatekeeper E274 and humanized PEACE motif helix are the structural bases of highly selective HDAC10 inhibitors [140]. These results conduct a useful model and support the development of HDACIs with reliable information.

Selective and non-selective HDAC10 inhibitors

Nowadays, many HDACIs exhibit potent broad-spectrum repression ability to HDACs (including HDAC10), examples in broad-spectrum HDACIs include suberoylanilide hydroxamic acid [141], CRA-024781 [142], CRA-026440 [143], AR42 [144], trichostatin A (TSA) [145], valproic acid (VPA) [146] and so on. Both CRA-024781 and CRA-026440 are novel hydroxamic acid-based HDACIs that show potency against a series of HDACs, including HDAC1, 2, 3, 6, 8 and 10. CRA-024781 and CRA-026440 have in vitro efficacy in suppressing tumor cell proliferation as well as angiogenesis, inducing apoptosis and inhibiting tumor growth in vivo [142,143]. Another group reported pan-HDACIs AR42 and sodium valproate, which also have great selectivity over HDAC1, 3, 8 and 10 and obvious anti-tumor properties were observed invivo and invitro following pre-treatment with these HDACIs. Notably, AR42 and sodium valproate diminish PD-L1 and PD-L2 expression, and consequently elevate the efficacy of pazopanib, which increases multiple immune cells, for instance M1 macrophage, neutrophils, NK cells and T cells [144]. In addition, TSA can inhibit HDAC10 and 6, and the selectivity over HDAC10 arises from its N-terminal domain [147]. In colorectal cancer cells, TSA induces the inhibition of HDAC10 as well as HDAC6, and subsequently attenuates the Wnt pathway by the deletion of the Wnt signaling pathway-associated factor TCF7L2 in a proteasome-dependent way, which suppresses cell proliferation in vitro [43]. Bufexamac, an anti-inflammatory drug screened out via a new protocol, is also selective for HDAC10 and HDAC6 and its cellular potency may rely on interferon-α secreted by mononuclear cells [148] (Figure 3).

Mechanisms of action of selective and non-selective HDAC10 inhibitors

Figure 3
Mechanisms of action of selective and non-selective HDAC10 inhibitors
Figure 3
Mechanisms of action of selective and non-selective HDAC10 inhibitors

However, due to some severe adverse effects of multitarget HDACIs [149], Géraldy et al. [150] investigated HDAC10-specific inhibitors and found that tubastatin A tightly bound to HDAC10 in HeLa cells with its basic amine in the cap group. Based on an HDAC10 homology model, they revealed that a hydrogen bond falls in between a cap group nitrogen, and a gatekeeper residue Glu272 contributes to the tight binding. Unfortunately, however, the development of a highly selective HDAC10 inhibitor is still far off because of the inability to abrogate HDAC6 activity.

Design or synthesis of HDAC10 inhibitors

We also examined previous works on the design or synthesis of HDAC10 inhibitors. By changing the condition of building block reaction, Villadsen et al. [151] synthesized azumamides A–E. In addition, they examined the inhibitory properties of HDAC10 under different drug concentrations (5 and 50 μM), which indicates both azumamides C and azumamides E markedly inhibit HDAC10. The HDACIs tubastatin A and PCI-34051 have the same N-benzylindole core [150,152]. After hybridizing these two inhibitors, Morgen et al. [153] synthesized dihydroxamic acids, which significantly suppressed the viability of neuroblastoma cells and played the role of potent inhibitor of HDAC10. Uba et al. [137] constructed M0017, the best model of human HDAC10, and filtered out ZINC19749069, the highest rank compound from the ZINC database, which displayed high stability when docking it into the catalytic channel of an HDAC10 model with quisinostat. Thus, M0017 and ZINC19749069 present considerable potential as an optimal HDACI and scaffold.

Although more and more studies could be reliably used for the HDACI designation, further exploration of the HDAC molecule structure and its biological characterization remain fundamental to shed light on the selection and development of the site-specific HDACIs.

Conclusion

Like other HDAC isoforms, HDAC10 exhibits various complex functions and clinic values [4,154,155]. As mentioned above, its functions involve in DNA damage repair, gene transcription and autophagy, and HDAC10-mediated tumor cell proliferation, apoptosis, invasion, migration, angiogenesis, metastasis and immune regulation, laying the theoretical foundation for clinical application. However, there are still challenges to be met. First, more details on the mechanisms of aberrant HDAC10 regulatory are essential to provide a more integrative understanding of HDAC10 and other HDACs. Besides, it is yet to be determined how to treat patients with HDACI resistance as well as the precise dose of HDACI. Furthermore, it remains unclear whether extending HDACI to other solid tumors would lead to satisfactory outcomes. With further in-depth study, HDAC10 may serve as an essential anti-tumor target and contribute to clinical applications in the future.

Data Availability

The present study includes no data deposited in external repositories.

Competing Interests

The authors declare that there are no competing interests associated with the manuscript.

Funding

The authors declare that there are no sources of funding to be acknowledged.

Author Contribution

B.Z. and F.j.C. drafted the manuscript. J.w.W., G.t.Z., Z.s.Y., Z.h.N. and W.H. revised the manuscript. All authors approved the final manuscript.

Acknowledgements

The authors gratefully thank the academic editor and the anonymous reviewers for their insightful comments and suggestions to improve this manuscript.

Abbreviations

     
  • AMPK

    AMP-activated protein kinase

  •  
  • AR

    androgen receptor

  •  
  • BAK

    BCL2 antagonist/killer

  •  
  • BCL2

    B-cell lymphoma-2

  •  
  • BETi

    bromodomain and extra-terminal protein inhibitor

  •  
  • BRD4

    bromodomain-containing protein 4

  •  
  • CMA

    chaperone-mediated autophagy

  •  
  • CRPC

    castration-resistant prostate cancer

  •  
  • CSC

    cancer stem cell

  •  
  • Cx43

    connexin 43

  •  
  • DUB3

    deubiquitinase ubiquitin-specific peptidase 17 like family member 2

  •  
  • ERK

    extracellular regulated protein kinase

  •  
  • E2

    estradiol

  •  
  • FSTL1

    follistatin-like 1

  •  
  • G6PD

    glucose-6-phosphate dehydrogenase

  •  
  • HCC

    hepatocellular cancer

  •  
  • HDAC

    histone deacetylase

  •  
  • HDACI

    HDAC inhibitor

  •  
  • HIV

    human immunodeficiency virus

  •  
  • Hsp

    heat shock protein

  •  
  • hSSB1

    human single-stranded DNA binding protein 1

  •  
  • IgAN

    immunoglobulin A nephropathy

  •  
  • KAP1

    KRAB-associated protein 1

  •  
  • KRAB

    kruppel-associated box domain

  •  
  • LH

    luteinizing hormone

  •  
  • LKB1

    liver kinase B1

  •  
  • MLH1

    mutL homolog 1

  •  
  • MMP

    matrix metalloproteinase

  •  
  • MMR

    mismatch repair system

  •  
  • MSH2

    mutS homolog 2

  •  
  • MTLE-HS

    mesial temporal lobe epilepsy with hippocampal sclerosis

  •  
  • NCOR2

    nuclear receptor co-repressor 2

  •  
  • NSCLC

    non-small-cell lung cancer

  •  
  • OS

    overall survival

  •  
  • Pax3

    paired box protein 3

  •  
  • PD-L1

    programmed cell death 1 ligand 1

  •  
  • PD-L2

    programmed cell death 1 ligand 2

  •  
  • PTEN22

    phosphatase and tensin homolog 22

  •  
  • SNP

    single nucleotide polymorphism

  •  
  • SOX9

    sex-determining region Y box protein 9

  •  
  • TCF7L2

    transcription factor 7 like 2

  •  
  • TGF-β

    transforming growth-factor β

  •  
  • TiO2

    titanium dioxide

  •  
  • Treg

    regulatory T cell

  •  
  • TSA

    trichostatin A

  •  
  • TXNIP

    thioredoxin interacting protein

  •  
  • VEGF

    vascular endothelial growth factor

  •  
  • VEGFR1

    vascular endothelial growth factor receptor 1/2

References

1.
Workman
J.L.
and
Kingston
R.E.
(
1998
)
Alteration of nucleosome structure as a mechanism of transcriptional regulation
.
Annu. Rev. Biochem.
67
,
545
579
[PubMed]
2.
Strahl
B.D.
and
Allis
C.D.
(
2000
)
The language of covalent histone modifications
.
Nature
403
,
41
45
[PubMed]
3.
Berger
S.L.
(
2001
)
An embarrassment of niches: the many covalent modifications of histones in transcriptional regulation
.
Oncogene
20
,
3007
3013
[PubMed]
4.
Chakrabarti
A.
,
Oehme
I.
,
Witt
O.
,
Oliveira
G.
,
Sippl
W.
,
Romier
C.
et al.
(
2015
)
HDAC8: a multifaceted target for therapeutic interventions
.
Trends Pharmacol. Sci.
36
,
481
492
[PubMed]
5.
Tong
J.J.
,
Liu
J.
,
Bertos
N.R.
and
Yang
X.J.
(
2002
)
Identification of HDAC10, a novel class II human histone deacetylase containing a leucine-rich domain
.
Nucleic Acids Res.
30
,
1114
1123
[PubMed]
6.
Hai
Y.
,
Shinsky
S.A.
,
Porter
N.J.
and
Christianson
D.W.
(
2017
)
Histone deacetylase 10 structure and molecular function as a polyamine deacetylase
.
Nat. Commun.
8
,
15368
[PubMed]
7.
Seto
E.
and
Yoshida
M.
(
2014
)
Erasers of histone acetylation: the histone deacetylase enzymes
.
Cold Spring Harb. Perspect. Biol.
6
,
a018713
8.
Caron
C.
,
Boyault
C.
and
Khochbin
S.
(
2005
)
Regulatory cross-talk between lysine acetylation and ubiquitination: role in the control of protein stability
.
BioEssays
27
,
408
415
9.
Fischle
W.
,
Wang
Y.
and
Allis
C.D.
(
2003
)
Histone and chromatin cross-talk
.
Curr. Opin. Cell Biol.
15
,
172
183
[PubMed]
10.
Leipe
D.D.
and
Landsman
D.
(
1997
)
Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily
.
Nucleic Acids Res.
25
,
3693
3697
[PubMed]
11.
Wang
P.
,
Wang
Z.
and
Liu
J.
(
2020
)
Role of HDACs in normal and malignant hematopoiesis
.
Mol. Can.
19
,
5
12.
Fischer
D.D.
,
Cai
R.
,
Bhatia
U.
,
Asselbergs
F.A.
,
Song
C.
,
Terry
R.
et al.
(
2002
)
Isolation and characterization of a novel class II histone deacetylase, HDAC10
.
J. Biol. Chem.
277
,
6656
6666
[PubMed]
13.
Kao
H.Y.
,
Lee
C.H.
,
Komarov
A.
,
Han
C.C.
and
Evans
R.M.
(
2002
)
Isolation and characterization of mammalian HDAC10, a novel histone deacetylase
.
J. Biol. Chem.
277
,
187
193
[PubMed]
14.
Guardiola
A.R.
and
Yao
T.P.
(
2002
)
Molecular cloning and characterization of a novel histone deacetylase HDAC10
.
J. Biol. Chem.
277
,
3350
3356
[PubMed]
15.
Grozinger
C.M.
and
Schreiber
S.L.
(
2000
)
Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization
.
Proc. Natl. Acad. Sci. U.S.A.
97
,
7835
7840
[PubMed]
16.
McKinsey
T.A.
,
Zhang
C.L.
,
Lu
J.
and
Olson
E.N.
(
2000
)
Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation
.
Nature
408
,
106
111
[PubMed]
17.
Verdin
E.
,
Dequiedt
F.
and
Kasler
H.G.
(
2003
)
Class II histone deacetylases: versatile regulators
.
Trends Genet.
19
,
286
293
18.
Hubbert
C.
,
Guardiola
A.
,
Shao
R.
,
Kawaguchi
Y.
,
Ito
A.
,
Nixon
A.
et al.
(
2002
)
HDAC6 is a microtubule-associated deacetylase
.
Nature
417
,
455
458
[PubMed]
19.
Shinsky
S.A.
and
Christianson
D.W.
(
2018
)
Polyamine deacetylase structure and catalysis: prokaryotic acetylpolyamine amidohydrolase and eukaryotic HDAC10
.
Biochemistry
57
,
3105
3114
[PubMed]
20.
Kao
H.Y.
,
Downes
M.
,
Ordentlich
P.
and
Evans
R.M.
(
2000
)
Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression
.
Genes Dev.
14
,
55
66
[PubMed]
21.
Zhou
X.
,
Richon
V.M.
,
Rifkind
R.A.
and
Marks
P.A.
(
2000
)
Identification of a transcriptional repressor related to the noncatalytic domain of histone deacetylases 4 and 5
.
Proc. Natl. Acad. Sci. U.S.A.
97
,
1056
1061
[PubMed]
22.
Finnin
M.S.
,
Donigian
J.R.
,
Cohen
A.
,
Richon
V.M.
,
Rifkind
R.A.
,
Marks
P.A.
et al.
(
1999
)
Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors
.
Nature
401
,
188
193
[PubMed]
23.
Wu
R.
,
Lu
Z.
,
Cao
Z.
and
Zhang
Y.
(
2011
)
Zinc chelation with hydroxamate in histone deacetylases modulated by water access to the linker binding channel
.
J. Am. Chem. Soc.
133
,
6110
6113
[PubMed]
24.
Gantt
S.L.
,
Joseph
C.G.
and
Fierke
C.A.
(
2010
)
Activation and inhibition of histone deacetylase 8 by monovalent cations
.
J. Biol. Chem.
285
,
6036
6043
[PubMed]
25.
Imai
S.
,
Armstrong
C.M.
,
Kaeberlein
M.
and
Guarente
L.
(
2000
)
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
.
Nature
403
,
795
800
[PubMed]
26.
Avalos
J.L.
,
Boeke
J.D.
and
Wolberger
C.
(
2004
)
Structural basis for the mechanism and regulation of Sir2 enzymes
.
Mol. Cell
13
,
639
648
[PubMed]
27.
Hanahan
D.
and
Weinberg
R.A.
(
2011
)
Hallmarks of cancer: the next generation
.
Cell
144
,
646
674
[PubMed]
28.
Hanahan
D.
and
Weinberg
R.A.
(
2000
)
The hallmarks of cancer
.
Cell
100
,
57
70
[PubMed]
29.
Yang
Y.
,
Huang
Y.
,
Wang
Z.
,
Wang
H.T.
,
Duan
B.
,
Ye
D.
et al.
(
2016
)
HDAC10 promotes lung cancer proliferation via AKT phosphorylation
.
Oncotarget
7
,
59388
59401
[PubMed]
30.
Li
Y.
,
Zhang
X.
,
Zhu
S.
,
Dejene
E.A.
,
Peng
W.
,
Sepulveda
A.
et al.
(
2020
)
HDAC10 regulates cancer stem-like cell properties in KRAS-driven lung adenocarcinoma
.
Cancer Res.
80
,
3265
3278
[PubMed]
31.
Fan
W.
,
Huang
J.
and
Xiao
H.
(
2015
)
Histone deacetylase 10 suppresses proliferation and invasion by inhibiting the phosphorylation of β-catenin and serves as an independent prognostic factor for human clear cell renal cell carcinoma
.
Int. J. Clin. Exp. Med.
8
,
3734
3742
[PubMed]
32.
Revathidevi
S.
and
Munirajan
A.K.
(
2019
)
Akt in cancer: mediator and more
.
Semin. Cancer Biol.
59
,
80
91
[PubMed]
33.
Guertin
D.A.
and
Sabatini
D.M.
(
2007
)
Defining the role of mTOR in cancer
.
Cancer Cell.
12
,
9
22
[PubMed]
34.
Shan
C.
,
Lu
Z.
,
Li
Z.
,
Sheng
H.
,
Fan
J.
,
Qi
Q.
et al.
(
2019
)
4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis
.
Cell Death Dis.
10
,
525
[PubMed]
35.
Evan
G.I.
and
Vousden
K.H.
(
2001
)
Proliferation, cell cycle and apoptosis in cancer
.
Nature
411
,
342
348
[PubMed]
36.
Li
Y.
,
Peng
L.
and
Seto
E.
(
2015
)
Histone deacetylase 10 regulates the cell cycle G2/M phase transition via a novel Let-7-HMGA2-cyclin A2 pathway
.
Mol. Cell. Biol.
35
,
3547
3565
[PubMed]
37.
Coqueret
O.
(
2003
)
New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment?
Trends Cell Biol.
13
,
65
70
[PubMed]
38.
Qie
S.
and
Diehl
J.A.
(
2016
)
Cyclin D1, cancer progression, and opportunities in cancer treatment
.
J. Mol. Med.
94
,
1313
1326
39.
Sutherland
R.L.
and
Musgrove
E.A.
(
2004
)
Cyclins and breast cancer
.
J. Mamm. Gland Biol. Neoplasia
9
,
95
104
[PubMed]
40.
Wong
R.S.
(
2011
)
Apoptosis in cancer: from pathogenesis to treatment
.
J. Exp. Clin. Cancer Res.
30
,
87
41.
Gross
A.
,
McDonnell
J.M.
and
Korsmeyer
S.J.
(
1999
)
BCL-2 family members and the mitochondria in apoptosis
.
Genes Dev.
13
,
1899
1911
[PubMed]
42.
Reed
J.C.
(
1997
)
Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies
.
Semin. Hematol.
34
,
9
19
[PubMed]
43.
Götze
S.
,
Coersmeyer
M.
,
Müller
O.
and
Sievers
S.
(
2014
)
Histone deacetylase inhibitors induce attenuation of Wnt signaling and TCF7L2 depletion in colorectal carcinoma cells
.
Int. J. Oncol.
45
,
1715
1723
[PubMed]
44.
Circu
M.L.
and
Aw
T.Y.
(
2010
)
Reactive oxygen species, cellular redox systems, and apoptosis
.
Free Radic. Biol. Med.
48
,
749
762
45.
Zorov
D.B.
,
Juhaszova
M.
and
Sollott
S.J.
(
2014
)
Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release
.
Physiol. Rev.
94
,
909
950
[PubMed]
46.
Lee
J.H.
,
Jeong
E.G.
,
Choi
M.C.
,
Kim
S.H.
,
Park
J.H.
,
Song
S.H.
et al.
(
2010
)
Inhibition of histone deacetylase 10 induces thioredoxin-interacting protein and causes accumulation of reactive oxygen species in SNU-620 human gastric cancer cells
.
Mol. Cells
30
,
107
112
[PubMed]
47.
Polacheck
W.J.
,
Zervantonakis
I.K.
and
Kamm
R.D.
(
2013
)
Tumor cell migration in complex microenvironments
.
Cell. Mol. Life Sci.
70
,
1335
1356
48.
Hamidi
H.
and
Ivaska
J.
(
2018
)
Every step of the way: integrins in cancer progression and metastasis
.
Nat. Rev. Cancer
18
,
533
548
[PubMed]
49.
Saiki
Y.
and
Horii
A.
(
2019
)
Multiple functions of S100A10, an important cancer promoter
.
Pathol. Int.
69
,
629
636
[PubMed]
50.
Castro-Castro
A.
,
Marchesin
V.
,
Monteiro
P.
,
Lodillinsky
C.
,
Rossé
C.
and
Chavrier
P.
(
2016
)
Cellular and molecular mechanisms of MT1-MMP-dependent cancer cell invasion
.
Annu. Rev. Cell Dev. Biol.
32
,
555
576
[PubMed]
51.
Cui
N.
,
Hu
M.
and
Khalil
R.A.
(
2017
)
Biochemical and biological attributes of matrix metalloproteinases
.
Prog. Mol. Biol. Transl. Sci.
147
,
1
73
[PubMed]
52.
Zhao
W.
,
Han
H.B.
and
Zhang
Z.Q.
(
2011
)
Suppression of lung cancer cell invasion and metastasis by connexin43 involves the secretion of follistatin-like 1 mediated via histone acetylation
.
Int. J. Biochem. Cell Biol.
43
,
1459
1468
[PubMed]
53.
Song
C.
,
Zhu
S.
,
Wu
C.
and
Kang
J.
(
2013
)
Histone deacetylase (HDAC) 10 suppresses cervical cancer metastasis through inhibition of matrix metalloproteinase (MMP) 2 and 9 expression
.
J. Biol. Chem.
288
,
28021
28033
[PubMed]
54.
Dong
Y.W.
,
Wang
R.
,
Cai
Q.Q.
,
Qi
B.
,
Wu
W.
,
Zhang
Y.H.
et al.
(
2014
)
Sulfatide epigenetically regulates miR-223 and promotes the migration of human hepatocellular carcinoma cells
.
J. Hepatol.
60
,
792
801
[PubMed]
55.
VON Schulz-Hausmann
S.A.
,
Schmeel
L.C.
,
Schmeel
F.C.
and
Schmidt-Wolf
I.G.
(
2014
)
Targeting the Wnt/beta-catenin pathway in renal cell carcinoma
.
Anticancer Res.
34
,
4101
4108
[PubMed]
56.
Shang
S.
,
Hua
F.
and
Hu
Z.W.
(
2017
)
The regulation of β-catenin activity and function in cancer: therapeutic opportunities
.
Oncotarget
8
,
33972
33989
[PubMed]
57.
Kerbel
R.
and
Folkman
J.
(
2002
)
Clinical translation of angiogenesis inhibitors
.
Nat. Rev. Cancer
2
,
727
739
[PubMed]
58.
Arias
H.R.
,
Richards
V.E.
,
Ng
D.
,
Ghafoori
M.E.
,
Le
V.
and
Mousa
S.A.
(
2009
)
Role of non-neuronal nicotinic acetylcholine receptors in angiogenesis
.
Int. J. Biochem. Cell Biol.
41
,
1441
1451
[PubMed]
59.
Rak
J.
,
Yu
J.L.
,
Klement
G.
and
Kerbel
R.S.
(
2000
)
Oncogenes and angiogenesis: signaling three-dimensional tumor growth
.
J. Investig. Dermatol. Symp. Proc.
5
,
24
33
[PubMed]
60.
Relf
M.
,
LeJeune
S.
,
Scott
P.A.
,
Fox
S.
,
Smith
K.
,
Leek
R.
et al.
(
1997
)
Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis
.
Cancer Res.
57
,
963
969
[PubMed]
61.
Duan
B.
,
Ye
D.
,
Zhu
S.
,
Jia
W.
,
Lu
C.
,
Wang
G.
et al.
(
2017
)
HDAC10 promotes angiogenesis in endothelial cells through the PTPN22/ERK axis
.
Oncotarget
8
,
61338
61349
[PubMed]
62.
Park
J.H.
,
Kim
S.H.
,
Choi
M.C.
,
Lee
J.
,
Oh
D.Y.
,
Im
S.A.
et al.
(
2008
)
Class II histone deacetylases play pivotal roles in heat shock protein 90-mediated proteasomal degradation of vascular endothelial growth factor receptors
.
Biochem. Biophys. Res. Commun.
368
,
318
322
[PubMed]
63.
Holohan
C.
,
Van Schaeybroeck
S.
,
Longley
D.B.
and
Johnston
P.G.
(
2013
)
Cancer drug resistance: an evolving paradigm
.
Nat. Rev. Cancer
13
,
714
726
[PubMed]
64.
Longley
D.B.
and
Johnston
P.G.
(
2005
)
Molecular mechanisms of drug resistance
.
J. Pathol.
205
,
275
292
[PubMed]
65.
Gottesman
M.M.
,
Fojo
T.
and
Bates
S.E.
(
2002
)
Multidrug resistance in cancer: role of ATP-dependent transporters
.
Nat. Rev. Cancer
2
,
48
58
[PubMed]
66.
Ridinger
J.
,
Koeneke
E.
,
Kolbinger
F.R.
,
Koerholz
K.
,
Mahboobi
S.
,
Hellweg
L.
et al.
(
2018
)
Dual role of HDAC10 in lysosomal exocytosis and DNA repair promotes neuroblastoma chemoresistance
.
Sci. Rep.
8
,
10039
[PubMed]
67.
Li
Y.J.
,
Lei
Y.H.
,
Yao
N.
,
Wang
C.R.
,
Hu
N.
,
Ye
W.C.
et al.
(
2017
)
Autophagy and multidrug resistance in cancer
.
Chin. J. Cancer
36
,
52
[PubMed]
68.
Oehme
I.
,
Linke
J.P.
,
Böck
B.C.
,
Milde
T.
,
Lodrini
M.
,
Hartenstein
B.
et al.
(
2013
)
Histone deacetylase 10 promotes autophagy-mediated cell survival
.
Proc. Natl. Acad. Sci. U.S.A.
110
,
E2592
E2601
[PubMed]
69.
Oehme
I.
,
Lodrini
M.
,
Brady
N.R.
and
Witt
O.
(
2013
)
Histone deacetylase 10-promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas
.
Autophagy
9
,
2163
2165
[PubMed]
70.
Islam
M.M.
,
Banerjee
T.
,
Packard
C.Z.
,
Kotian
S.
,
Selvendiran
K.
,
Cohn
D.E.
et al.
(
2017
)
HDAC10 as a potential therapeutic target in ovarian cancer
.
Gynecol. Oncol.
144
,
613
620
[PubMed]
71.
Bartkova
J.
,
Horejsí
Z.
,
Koed
K.
,
Krämer
A.
,
Tort
F.
,
Zieger
K.
et al.
(
2005
)
DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
.
Nature
434
,
864
870
[PubMed]
72.
Richard
D.J.
,
Savage
K.
,
Bolderson
E.
,
Cubeddu
L.
,
So
S.
,
Ghita
M.
et al.
(
2011
)
hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex
.
Nucleic Acids Res.
39
,
1692
1702
[PubMed]
73.
Wu
Y.
,
Chen
H.
,
Lu
J.
,
Zhang
M.
,
Zhang
R.
,
Duan
T.
et al.
(
2015
)
Acetylation-dependent function of human single-stranded DNA binding protein 1
.
Nucleic Acids Res.
43
,
7878
7887
[PubMed]
74.
Shafi
A.A.
,
Yen
A.E.
and
Weigel
N.L.
(
2013
)
Androgen receptors in hormone-dependent and castration-resistant prostate cancer
.
Pharmacol. Ther.
140
,
223
238
75.
Welti
J.
,
Sharp
A.
,
Yuan
W.
,
Dolling
D.
,
Nava Rodrigues
D.
,
Figueiredo
I.
et al.
(
2018
)
Targeting bromodomain and extra-terminal (BET) family proteins in castration-resistant prostate cancer (CRPC)
.
Clin. Cancer Res.
24
,
3149
3162
76.
Dai
X.
,
Gan
W.
,
Li
X.
,
Wang
S.
,
Zhang
W.
,
Huang
L.
et al.
(
2017
)
Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4
.
Nat. Med.
23
,
1063
1071
[PubMed]
77.
Jin
X.
,
Yan
Y.
,
Wang
D.
,
Ding
D.
,
Ma
T.
,
Ye
Z.
et al.
(
2018
)
DUB3 Promotes BET Inhibitor Resistance and Cancer Progression by Deubiquitinating BRD4
.
Mol. Cell
71
,
592.e4
605.e4
[PubMed]
78.
Sun
H.
,
Mediwala
S.N.
,
Szafran
A.T.
,
Mancini
M.A.
and
Marcelli
M.
(
2016
)
CUDC-101, a novel inhibitor of full-length androgen receptor (flAR) and androgen receptor variant 7 (AR-V7) activity: mechanism of action and in vivo efficacy
.
Hormones Cancer
7
,
196
210
[PubMed]
79.
Saygin
C.
,
Matei
D.
,
Majeti
R.
,
Reizes
O.
and
Lathia
J.D.
(
2019
)
Targeting cancer stemness in the clinic: from hype to hope
.
Cell Stem Cell
24
,
25
40
[PubMed]
80.
Batlle
E.
and
Clevers
H.
(
2017
)
Cancer stem cells revisited
.
Nat. Med.
23
,
1124
1134
[PubMed]
81.
Guo
W.
,
Keckesova
Z.
,
Donaher
J.L.
,
Shibue
T.
,
Tischler
V.
,
Reinhardt
F.
et al.
(
2012
)
Slug and Sox9 cooperatively determine the mammary stem cell state
.
Cell
148
,
1015
1028
[PubMed]
82.
Ye
X.
,
Tam
W.L.
,
Shibue
T.
,
Kaygusuz
Y.
,
Reinhardt
F.
,
Ng Eaton
E.
et al.
(
2015
)
Distinct EMT programs control normal mammary stem cells and tumour-initiating cells
.
Nature
525
,
256
260
[PubMed]
83.
Dahiya
S.
,
Beier
U.H.
,
Wang
L.
,
Han
R.
,
Jiao
J.
,
Akimova
T.
et al.
(
2020
)
HDAC10 deletion promotes Foxp3 (+) T-regulatory cell function
.
Sci. Rep.
10
,
424
[PubMed]
84.
Chen
Y.
,
Song
Y.
,
Du
W.
,
Gong
L.
,
Chang
H.
and
Zou
Z.
(
2019
)
Tumor-associated macrophages: an accomplice in solid tumor progression
.
J. Biomed. Sci.
26
,
78
[PubMed]
85.
Kaushik
S.
and
Cuervo
A.M.
(
2018
)
The coming of age of chaperone-mediated autophagy
.
Nat. Rev. Mol. Cell Biol.
19
,
365
381
[PubMed]
86.
Obayashi
H.
,
Nagano
Y.
,
Takahashi
T.
,
Seki
T.
,
Tanaka
S.
,
Sakai
N.
et al.
(
2020
)
Histone deacetylase 10 knockout activates chaperone-mediated autophagy and accelerates the decomposition of its substrate
.
Biochem. Biophys. Res. Commun.
523
,
246
252
[PubMed]
87.
Arias
E.
(
2017
)
Methods to study chaperone-mediated autophagy
.
Methods Enzymol.
588
,
283
305
[PubMed]
88.
Kaushik
S.
and
Cuervo
A.M.
(
2009
)
Methods to monitor chaperone-mediated autophagy
.
Methods Enzymol.
452
,
297
324
[PubMed]
89.
Baretti
M.
and
Le
D.T.
(
2018
)
DNA mismatch repair in cancer
.
Pharmacol. Ther.
189
,
45
62
90.
Li
G.M.
(
2008
)
Mechanisms and functions of DNA mismatch repair
.
Cell Res.
18
,
85
98
[PubMed]
91.
Radhakrishnan
R.
,
Li
Y.
,
Xiang
S.
,
Yuan
F.
,
Yuan
Z.
,
Telles
E.
et al.
(
2015
)
Histone deacetylase 10 regulates DNA mismatch repair and may involve the deacetylation of MutS homolog 2
.
J. Biol. Chem.
290
,
22795
22804
[PubMed]
92.
Tao
X.
,
Yan
Y.
,
Lu
L.
and
Chen
B.
(
2017
)
HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma
.
Oncol. Lett.
14
,
4923
4929
[PubMed]
93.
Park
B.L.
,
Kim
Y.J.
,
Cheong
H.S.
,
Lee
S.O.
,
Han
C.S.
,
Yoon
J.H.
et al.
(
2007
)
HDAC10 promoter polymorphism associated with development of HCC among chronic HBV patients
.
Biochem. Biophys. Res. Commun.
363
,
776
781
[PubMed]
94.
Fonseca
A.L.
,
Kugelberg
J.
,
Starker
L.F.
,
Scholl
U.
,
Choi
M.
,
Hellman
P.
et al.
(
2012
)
Comprehensive DNA methylation analysis of benign and malignant adrenocortical tumors
.
Genes Chromosomes Cancer
51
,
949
960
[PubMed]
95.
Uzdensky
A.
,
Demyanenko
S.
,
Bibov
M.
,
Sharifulina
S.
,
Kit
O.
,
Przhedetski
Y.
et al.
(
2014
)
Expression of proteins involved in epigenetic regulation in human cutaneous melanoma and peritumoral skin
.
Tumour Biol.
35
,
8225
8233
96.
Kasaian
K.
,
Wiseman
S.M.
,
Walker
B.A.
,
Schein
J.E.
,
Zhao
Y.
,
Hirst
M.
et al.
(
2015
)
The genomic and transcriptomic landscape of anaplastic thyroid cancer: implications for therapy
.
BMC Cancer
15
,
984
[PubMed]
97.
Lourdusamy
A.
,
Rahman
R.
and
Grundy
R.G.
(
2015
)
Expression alterations define unique molecular characteristics of spinal ependymomas
.
Oncotarget
6
,
19780
19791
[PubMed]
98.
Osada
H.
,
Tatematsu
Y.
,
Saito
H.
,
Yatabe
Y.
,
Mitsudomi
T.
and
Takahashi
T.
(
2004
)
Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients
.
Int. J. Cancer
112
,
26
32
[PubMed]
99.
Jin
Z.
,
Jiang
W.
,
Jiao
F.
,
Guo
Z.
,
Hu
H.
,
Wang
L.
et al.
(
2014
)
Decreased expression of histone deacetylase 10 predicts poor prognosis of gastric cancer patients
.
Int. J. Clin. Exp. Pathol.
7
,
5872
5879
[PubMed]
100.
Liu
X.
,
Wang
Y.
,
Zhang
R.
,
Jin
T.
,
Qu
L.
,
Jin
Q.
et al.
(
2020
)
HDAC10 is positively associated with PD-L1 expression and poor prognosis in patients with NSCLC
.
Front. Oncol.
10
,
485
[PubMed]
101.
Van Damme
M.
,
Crompot
E.
,
Meuleman
N.
,
Mineur
P.
,
Bron
D.
,
Lagneaux
L.
et al.
(
2012
)
HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance
.
Epigenetics
7
,
1403
1412
[PubMed]
102.
Wang
J.C.
,
Kafeel
M.I.
,
Avezbakiyev
B.
,
Chen
C.
,
Sun
Y.
,
Rathnasabapathy
C.
et al.
(
2011
)
Histone deacetylase in chronic lymphocytic leukemia
.
Oncology
81
,
325
329
[PubMed]
103.
De Rossi
G.
,
Marroni
P.
,
Paganuzzi
M.
,
Mauro
F.R.
,
Tenca
C.
,
Zarcone
D.
et al.
(
1997
)
Increased serum levels of soluble CD44 standard, but not of variant isoforms v5 and v6, in B cell chronic lymphocytic leukemia
.
Leukemia
11
,
134
141
[PubMed]
104.
De Rossi
G.
,
Zarcone
D.
,
Mauro
F.
,
Cerruti
G.
,
Tenca
C.
,
Puccetti
A.
et al.
(
1993
)
Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: malignant cell phenotypes define distinct disease subsets
.
Blood
81
,
2679
2687
[PubMed]
105.
Dermani
F.K.
,
Samadi
P.
,
Rahmani
G.
,
Kohlan
A.K.
and
Najafi
R.
(
2019
)
PD-1/PD-L1 immune checkpoint: Potential target for cancer therapy
.
J. Cell. Physiol.
234
,
1313
1325
[PubMed]
106.
Kim
J.H.
,
Moon
S.H.
,
No
M.
,
Kim
J.J.
,
Choi
E.J.
,
Cho
B.J.
et al.
(
2016
)
Isotype-specific inhibition of histone deacetylases: identification of optimal targets for radiosensitization
.
Cancer Res. Treat.
48
,
1130
1140
107.
Zhang
H.P.
,
Wang
L.
,
Fu
J.J.
,
Fan
T.
,
Wang
Z.L.
and
Wang
G.
(
2016
)
Association between histone hyperacetylation status in memory T lymphocytes and allergen-induced eosinophilic airway inflammation
.
Respirology
21
,
850
857
[PubMed]
108.
Rocco
L.
,
Santonastaso
M.
,
Mottola
F.
,
Costagliola
D.
,
Suero
T.
,
Pacifico
S.
et al.
(
2015
)
Genotoxicity assessment of TiO2 nanoparticles in the teleost Danio rerio
.
Ecotoxicol. Environ. Saf.
113
,
223
230
[PubMed]
109.
Jayaram
D.T.
and
Payne
C.K.
(
2020
)
Food-grade TiO (2) particles generate intracellular superoxide and alter epigenetic modifiers in human lung cells
.
Chem. Res. Toxicol.
33
,
2872
2879
[PubMed]
110.
Choi
J.S.
,
Lee
W.J.
,
Baik
S.H.
,
Yoon
H.K.
,
Lee
K.H.
,
Kim
Y.H.
et al.
(
2009
)
Array CGH reveals genomic aberrations in human emphysema
.
Lung
187
,
165
172
[PubMed]
111.
Choi
S.Y.
,
Piao
Z.H.
,
Jin
L.
,
Kim
J.H.
,
Kim
G.R.
,
Ryu
Y.
et al.
(
2016
)
Piceatannol attenuates renal fibrosis induced by unilateral ureteral obstruction via downregulation of histone deacetylase 4/5 or p38-MAPK signaling
.
PLoS ONE
11
,
e0167340
[PubMed]
112.
Guo
Y.
,
Gao
W.
,
Wang
D.
,
Liu
W.
and
Liu
Z.
(
2018
)
Gene alterations in monocytes are pathogenic factors for immunoglobulin a nephropathy by bioinformatics analysis of microarray data
.
BMC Nephrol.
19
,
184
[PubMed]
113.
Kebir
O.
,
Chaumette
B.
,
Fatjó-Vilas
M.
,
Ambalavanan
A.
,
Ramoz
N.
,
Xiong
L.
et al.
(
2014
)
Family-based association study of common variants, rare mutation study and epistatic interaction detection in HDAC genes in schizophrenia
.
Schizophr. Res.
160
,
97
103
[PubMed]
114.
Kim
T.
,
Park
J.K.
,
Kim
H.J.
,
Chung
J.H.
and
Kim
J.W.
(
2010
)
Association of histone deacetylase genes with schizophrenia in Korean population
.
Psychiatry Res.
178
,
266
269
[PubMed]
115.
Wang
L.
,
Zheng
S.
,
Zhang
L.
,
Xiao
H.
,
Gan
H.
,
Chen
H.
et al.
(
2020
)
Histone deacetylation 10 alleviates inflammation after intracerebral hemorrhage via the PTPN22/NLRP3 pathway in rats
.
Neuroscience
432
,
247
259
[PubMed]
116.
González
B.
,
Bernardi
A.
,
Torres
O.V.
,
Jayanthi
S.
,
Gomez
N.
,
Sosa
M.H.
et al.
(
2020
)
HDAC superfamily promoters acetylation is differentially regulated by modafinil and methamphetamine in the mouse medial prefrontal cortex
.
Addict. Biol.
25
,
e12737
[PubMed]
117.
Xin
M.
,
Yue
T.
,
Ma
Z.
,
Wu
F.F.
,
Gow
A.
and
Lu
Q.R.
(
2005
)
Myelinogenesis and axonal recognition by oligodendrocytes in brain are uncoupled in Olig1-null mice
.
J. Neurosci.
25
,
1354
1365
118.
Lu
Q.R.
,
Sun
T.
,
Zhu
Z.
,
Ma
N.
,
Garcia
M.
,
Stiles
C.D.
et al.
(
2002
)
Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection
.
Cell
109
,
75
86
[PubMed]
119.
Dai
J.
,
Bercury
K.K.
,
Jin
W.
and
Macklin
W.B.
(
2015
)
Olig1 acetylation and nuclear export mediate oligodendrocyte development
.
J. Neurosci.
35
,
15875
15893
120.
Srivastava
A.
,
Banerjee
J.
,
Dubey
V.
,
Tripathi
M.
,
Chandra
P.S.
,
Sharma
M.C.
et al.
(
2020
)
Role of altered expression, activity and sub-cellular distribution of various histone deacetylases (HDACs) in mesial temporal lobe epilepsy with hippocampal sclerosis
.
Cell. Mol. Neurobiol.
121.
Xu
W.
,
An
X.
,
Zhang
N.
,
Li
L.
,
Zhang
X.
,
Wang
Y.
et al.
(
2019
)
Middle-aged female rats lack changes in histone H3 acetylation in the anterior hypothalamus observed in young females on the day of a luteinizing hormone surge
.
Biosci. Trends
13
,
334
341
[PubMed]
122.
Lai
I.L.
,
Lin
T.P.
,
Yao
Y.L.
,
Lin
C.Y.
,
Hsieh
M.J.
and
Yang
W.M.
(
2010
)
Histone deacetylase 10 relieves repression on the melanogenic program by maintaining the deacetylation status of repressors
.
J. Biol. Chem.
285
,
7187
7196
[PubMed]
123.
Qian
H.
,
Chen
Y.
,
Nian
Z.
,
Su
L.
,
Yu
H.
,
Chen
F.J.
et al.
(
2017
)
HDAC6-mediated acetylation of lipid droplet-binding protein CIDEC regulates fat-induced lipid storage
.
J. Clin. Invest.
127
,
1353
1369
[PubMed]
124.
Funato
H.
,
Oda
S.
,
Yokofujita
J.
,
Igarashi
H.
and
Kuroda
M.
(
2011
)
Fasting and high-fat diet alter histone deacetylase expression in the medial hypothalamus
.
PLoS ONE
6
,
e18950
[PubMed]
125.
Sonkar
R.
,
Powell
C.A.
and
Choudhury
M.
(
2016
)
Benzyl butyl phthalate induces epigenetic stress to enhance adipogenesis in mesenchymal stem cells
.
Mol. Cell. Endocrinol.
431
,
109
122
[PubMed]
126.
Fanales-Belasio
E.
,
Raimondo
M.
,
Suligoi
B.
and
Buttò
S.
(
2010
)
HIV virology and pathogenetic mechanisms of infection: a brief overview
.
Annali Dell’Istituto Superiore Di Sanita
46
,
5
14
[PubMed]
127.
Ran
X.
,
Ao
Z.
,
Trajtman
A.
,
Xu
W.
,
Kobinger
G.
,
Keynan
Y.
et al.
(
2017
)
HIV-1 envelope glycoprotein stimulates viral transcription and increases the infectivity of the progeny virus through the manipulation of cellular machinery
.
Sci. Rep.
7
,
9487
[PubMed]
128.
Ran
X.
,
Ao
Z.
,
Olukitibi
T.
and
Yao
X.
(
2019
)
Characterization of the role of host cellular factor histone deacetylase 10 during HIV-1 replication
.
Viruses
12
,
28
[PubMed]
129.
Rodriguez
M.
,
Lapierre
J.
,
Ojha
C.R.
,
Pawitwar
S.
,
Karuppan
M.K.M.
,
Kashanchi
F.
et al.
(
2019
)
Morphine counteracts the antiviral effect of antiretroviral drugs and causes upregulation of p62/SQSTM1 and histone-modifying enzymes in HIV-infected astrocytes
.
J. Neurovirol.
25
,
263
274
[PubMed]
130.
Samji
H.
,
Cescon
A.
,
Hogg
R.S.
,
Modur
S.P.
,
Althoff
K.N.
,
Buchacz
K.
et al.
(
2013
)
Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada
.
PLoS ONE
8
,
e81355
[PubMed]
131.
Pinto
G.
,
Shtaif
B.
,
Phillip
M.
and
Gat-Yablonski
G.
(
2016
)
Growth attenuation is associated with histone deacetylase 10-induced autophagy in the liver
.
J. Nutr. Biochem.
27
,
171
180
[PubMed]
132.
Liao
W.
,
Sun
J.
,
Liu
W.
,
Li
W.
,
Jia
J.
,
Ou
F.
et al.
(
2019
)
HDAC10 upregulation contributes to interleukin 1β-mediated inflammatory activation of synovium-derived mesenchymal stem cells in temporomandibular joint
.
J. Cell. Physiol.
234
,
12646
12662
[PubMed]
133.
Luzzani
C.
,
Solari
C.
,
Losino
N.
,
Ariel
W.
,
Romorini
L.
,
Bluguermann
C.
et al.
(
2011
)
Modulation of chromatin modifying factors’ gene expression in embryonic and induced pluripotent stem cells
.
Biochem. Biophys. Res. Commun.
410
,
816
822
[PubMed]
134.
Schlüter
A.
,
Aksan
B.
,
Fioravanti
R.
,
Valente
S.
,
Mai
A.
and
Mauceri
D.
(
2019
)
Histone deacetylases contribute to excitotoxicity-triggered degeneration of retinal ganglion cells in vivo
.
Mol. Neurobiol.
56
,
8018
8034
[PubMed]
135.
Seo
S.M.
,
Koh
Y.S.
,
Jung
H.O.
,
Choi
J.S.
,
Kim
P.J.
,
Baek
S.H.
et al.
(
2011
)
Deoxyribonucleic acid copy number aberrations in vasospastic angina patients using an array comparative genomic hybridization
.
Korean Circ. J.
41
,
385
393
136.
Uba
A.I.
and
Yelekçi
K.
(
2020
)
Crystallographic structure versus homology model: a case study of molecular dynamics simulation of human and zebrafish histone deacetylase 10
.
J. Biomol. Struct. Dyn.
38
,
4397
4406
137.
Ibrahim Uba
A.
and
Yelekçi
K.
(
2019
)
Homology modeling of human histone deacetylase 10 and design of potential selective inhibitors
.
J. Biomol. Struct. Dyn.
37
,
3627
3636
138.
Thangapandian
S.
,
John
S.
,
Lee
Y.
,
Arulalapperumal
V.
and
Lee
K.W.
(
2012
)
Molecular modeling study on tunnel behavior in different histone deacetylase isoforms
.
PLoS ONE
7
,
e49327
[PubMed]
139.
Herbst-Gervasoni
C.J.
and
Christianson
D.W.
(
2019
)
Binding of N (8)-acetylspermidine analogues to histone deacetylase 10 reveals molecular strategies for blocking polyamine deacetylation
.
Biochemistry
58
,
4957
4969
[PubMed]
140.
Herbst-Gervasoni
C.J.
,
Steimbach
R.R.
,
Morgen
M.
,
Miller
A.K.
and
Christianson
D.W.
(
2020
)
Structural basis for the selective inhibition of HDAC10, the cytosolic polyamine deacetylase
.
ACS Chem. Biol.
15
,
2154
2163
[PubMed]
141.
Codd
R.
,
Braich
N.
,
Liu
J.
,
Soe
C.Z.
and
Pakchung
A.A.
(
2009
)
Zn (II)-dependent histone deacetylase inhibitors: suberoylanilide hydroxamic acid and trichostatin A
.
Int. J. Biochem. Cell Biol.
41
,
736
739
[PubMed]
142.
Buggy
J.J.
,
Cao
Z.A.
,
Bass
K.E.
,
Verner
E.
,
Balasubramanian
S.
,
Liu
L.
et al.
(
2006
)
CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo
.
Mol. Cancer Ther.
5
,
1309
1317
[PubMed]
143.
Cao
Z.A.
,
Bass
K.E.
,
Balasubramanian
S.
,
Liu
L.
,
Schultz
B.
,
Verner
E.
et al.
(
2006
)
CRA-026440: a potent, broad-spectrum, hydroxamic histone deacetylase inhibitor with antiproliferative and antiangiogenic activity in vitro and in vivo
.
Mol. Cancer Ther.
5
,
1693
1701
[PubMed]
144.
Booth
L.
,
Roberts
J.L.
,
Poklepovic
A.
,
Kirkwood
J.
and
Dent
P.
(
2017
)
HDAC inhibitors enhance the immunotherapy response of melanoma cells
.
Oncotarget
8
,
83155
83170
[PubMed]
145.
De Souza
C.
and
Chatterji
B.P.
(
2015
)
HDAC inhibitors as novel anti-cancer therapeutics
.
Recent Patents on Anti-cancer Drug Discovery
10
,
145
162
[PubMed]
146.
Gurvich
N.
,
Tsygankova
O.M.
,
Meinkoth
J.L.
and
Klein
P.S.
(
2004
)
Histone deacetylase is a target of valproic acid-mediated cellular differentiation
.
Cancer Res.
64
,
1079
1086
[PubMed]
147.
Brush
M.H.
,
Guardiola
A.
,
Connor
J.H.
,
Yao
T.P.
and
Shenolikar
S.
(
2004
)
Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases
.
J. Biol. Chem.
279
,
7685
7691
[PubMed]
148.
Bantscheff
M.
,
Hopf
C.
,
Savitski
M.M.
,
Dittmann
A.
,
Grandi
P.
,
Michon
A.M.
et al.
(
2011
)
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes
.
Nat. Biotechnol.
29
,
255
265
[PubMed]
149.
Roche
J.
and
Bertrand
P.
(
2016
)
Inside HDACs with more selective HDAC inhibitors
.
Eur. J. Med. Chem.
121
,
451
483
[PubMed]
150.
Géraldy
M.
,
Morgen
M.
,
Sehr
P.
,
Steimbach
R.R.
,
Moi
D.
,
Ridinger
J.
et al.
(
2019
)
Selective inhibition of histone deacetylase 10: hydrogen bonding to the gatekeeper residue is implicated
.
J. Med. Chem.
62
,
4426
4443
[PubMed]
151.
Villadsen
J.S.
,
Stephansen
H.M.
,
Maolanon
A.R.
,
Harris
P.
and
Olsen
C.A.
(
2013
)
Total synthesis and full histone deacetylase inhibitory profiling of Azumamides A-E as well as β²- epi-Azumamide E and β³-epi-Azumamide E
.
J. Med. Chem.
56
,
6512
6520
[PubMed]
152.
Balasubramanian
S.
,
Ramos
J.
,
Luo
W.
,
Sirisawad
M.
,
Verner
E.
and
Buggy
J.J.
(
2008
)
A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas
.
Leukemia
22
,
1026
1034
[PubMed]
153.
Morgen
M.
,
Steimbach
R.R.
,
Géraldy
M.
,
Hellweg
L.
,
Sehr
P.
,
Ridinger
J.
et al.
(
2020
)
Design and synthesis of dihydroxamic acids as HDAC6/8/10 inhibitors
.
Chem. Med. Chem.
15
,
1163
1174
154.
Li
T.
,
Zhang
C.
,
Hassan
S.
,
Liu
X.
,
Song
F.
,
Chen
K.
et al.
(
2018
)
Histone deacetylase 6 in cancer
.
J. Hematol. Oncol.
11
,
111
[PubMed]
155.
Liu
S.S.
,
Wu
F.
,
Jin
Y.M.
,
Chang
W.Q.
and
Xu
T.M.
(
2020
)
HDAC11: a rising star in epigenetics
.
Biomed. Pharmacother.
131
,
110607
[PubMed]

Author notes

*

These authors contributed equally to this work.

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