Several studies on the prognostic value of microRNA 142 (miR-142) in solid tumors have reported conflicting results. Therefore, the aim of this meta-analysis was to evaluate the relationship between the miR-142 and prognosis in solid tumors. A comprehensive search for relevant studies was conducted until 10 November 2020. Studies that investigated the prognostic significance of the miR-142 in solid tumors were included. The hazard ratio and 95% confidence interval were calculated using a random-effects model. All data analyses were performed using the STATA 12.0 software (Stata Corporation, College Station, TX, U.S.A.). Twenty articles involving 2451 participants were included in the meta-analysis. The results showed that high miR-142 expression was a better predictor of overall survival (OS) (HR = 0.66, 95% CI: 0.47–0.93) and disease-free/progression-free/recurrence-free survival (DFS/PFS/RFS) (HR = 0.71, 95% CI: 0.55–0.91) compared with low miR-142 expression. MiR-142 can be used as an effective prognostic marker for patients with solid tumors. Future large prospective studies are warranted to further confirm the present findings.

Background: Both meta-analyses and systematic reviews were used to assess the relationship between purinergic receptor P2X ligand-gated ion channel 7 ( P2RX7 ) rs3751143 polymorphism and the risk of cancer. Materials and methods: The data used in this research were collected from Google Scholar, Web of Science, CNKI, and Wan Fang Data databases. The final retrieval ended on 22 February 2019. The strength of correlation was assessed using odds ratios and 95% confidence intervals. Based on the heterogeneity test results, fixed-effect (Mantel–Haenszel) or random-effects (DerSimonian–Laird) models were selected to summarise the collective effects. Results: Eight separate studies containing 1462 cancer cases and 3037 controls were enrolled. Overall, there was no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, or recessive models. Conclusions: Our meta-analysis indicates that there is no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, and recessive models.

Background: Several studies have assessed the relationship between long non-coding RNA five prime to Xist (FTX) expression, clinicopathological features, and survival outcomes in patients with cancer with conflicting results. This meta-analysis synthesized existing data to clarify the association between FTX with cancer prognosis. Methods: PubMed, Embase, Cochrane library, Web of Science, Chinese CNKI, and the Chinese WanFang databases were used to search for relevant studies. The role of FTX in cancers was evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Eleven studies comprising 1210 participants including colorectal cancer (CRC), hepatocellular carcinoma (HCC), gastric cancer (GC), renal cell carcinoma (RCC), osteosarcoma (OSC), and glioma were enrolled in this analysis. The meta-analysis showed that high FTX expression was significantly associated with several clinicopathological characteristics, including lymph node metastasis in patients with CRC, GC, HCC, and RCC, distant metastasis in patients with CRC, GC, HCC, and OSC, larger tumor size in patients with CRC, GC, HCC, RCC, and OSC, and subsequently TNM/clinical stage in patients with CRC, GC, HCC, OSC, and glioma. The pooled results from the survival analysis revealed a significant correlation between high FTX expression and shorter OS in patients with HCC, CRC, GC, OSC, and glioma. Further, FTX overexpression could be an independent predictive marker for shorter OS in patients with CRC, HCC, OSC, and glioma. Conclusions: FTX may be a potential oncogene, with high FTX expression being associated with a poorer prognosis in patients with CRC, HCC, OSC, and glioma.

MicroRNA-196a (miR-196a) was previously reported to be up-regulated in cancers, and it has the diagnostic and prognostic values in cancers. Whereas, the conclusion was still unclear according to the published data. To assess such roles of miR-196a in cancers, the present study was conducted based on published data and online cancer-related databases. To identify the relevant published data, we searched articles in databases and then the relevant data were extracted to evaluate the correlation between miR-196a expression and diagnosis, prognosis for cancer patients. The pooled results showed that miR-196a was a valuable diagnostic biomarker in cancer (area under curve (AUC) = 0.87, 95% CI: 0.84–0.90; sensitivity (SEN) = 0.73, 95% CI: 0.64–0.81; specificity (SPE) = 0.90, 95% CI: 0.81–0.95), which was consistent with the data from databases (breast cancer: miR-196a-3p: AUC = 0.77, 95% CI: 0.74–0.79; miR-196a-5p: AUC = 0.71, 95% CI: 0.66–0.75; pancreatic cancer: miR-196a-3p: AUC = 0.80, 95% CI: 0.73–0.87; miR-196a-5p: AUC = 0.61, 95% CI: 0.51–0.71). In addition, the pooled result revealed that elevated miR-196a expression in tumor tissues (HR = 2.54, 95% CI: 1.79–3.61, P Heterogeneity =0.000, I 2 = 75.8%) or serum/plasma (HR = 4.06, 95% CI: 2.67–6.18, P Heterogeneity =0.668, I 2 = 0%) of patients was an unfavorable survival biomarker, which was consistent with the data from databases (adrenocortical carcinoma: HR = 5.70; esophageal carcinoma: HR = 1.93; brain lower grade glioma: HR = 2.91; GSE40267: HR = 2.47, 95% CI: 1.2–5.07; TCGA: HR = 1.82, 95% CI: 1.21–2.74; GSE19783: HR = 4.24, 95% CI: 1–18.06). In short, our results demonstrated that miR-196a in tumor tissue or serum/plasma could be used as a prognostic and diagnostic values for cancers.

Background: In recent years, the annual incidence of thyroid cancer (TC) has increased, with papillary thyroid cancer (PTC) identified as the most commonwinwordpathological type accounting for approximately 80% of all thyroid cancer cases. The tumor microenvironment is known to play a vital role in tumor information transmission and immune detection. Methods: In the present study, we examined gene expression data from 518 patients with PTC. The ESTIMATE algorithm was used to calculate immune and stromal scores of PTC patients. Based on a protein–protein interaction (PPI) network, functional enrichment and overall survival analyses, C-X-C motif chemokine ligand 10 (CXCL10) was identified as a core gene. We further investigated the roles of core genes of PTC in the tumor immune microenvironment using LinkedOmics, GSEA, and TIMER tools. Results: Immune, stromal and ESTIMATE scores were related to clinicopathological variables of patients with PTC, but not survival outcomes. Eight differentially expressed genes (DEGs) were associated with survival outcome. In addition, immunochemical staining experiments revealed lower expression of CXCL10 in PTC than paracancerous tissues. GSEA pathway enrichment analysis revealed downregulation of CXCL10 in multiple cancer pathways. CXCL10 and related genes were enriched in pathways related to adaptive immune response, cellular defense response and regulation of innate immune response. Conclusion: The tumor microenvironment plays a critical role in development of PTC and CXCL10 may serve as a novel target of precision therapy for this patient population.

Background: Head and neck squamous cell carcinoma (HNSCC) is recognised as an immune active cancer, but little is known about the role of microRNAs (miRNAs) in it. In the present study, we aim to determine a prognostic and immune-related miRNAs signature (IRMS) in HNSCC. Methods: Spearman correlation analysis was used to screen out prognostic immune-related miRNAs based on single-sample gene set enrichment analysis (ssGSEA). Least absolute shrinkage and selection operator (LASSO) Cox regression model was used to establish IRMS in HNSCC. Then, the influence of the IRMS on HNSCC was comprehensively analysed. Results: We obtained 11 prognostic immune-related miRNAs based on ssGSEA. Then an IRMS integrated with six miRNAs was established through LASSO Cox regression analysis. The stratification survival analysis indicated that IRMS was independent from other characteristics and performed favourably in the overall survival (OS) prediction. The function annotation suggested that IRMS was highly associated with the immune-related response biological processes and pathways which are so important for tumorigenesis of HNSCC. Moreover, the nomogram demonstrated that our model was identified as an independent prognostic factor. In addition, we found that IRMS was significantly correlated with the immune infiltration and expression of critical immune checkpoints, indicating that the poor prognosis might be caused partly by immunosuppressive microenvironment. Conclusion: We established a novel IRMS, which exhibited a potent prognostic value and could be representative of immune status in HNSCC.

Cancer immunotherapy has recently undergone rapid development into a validated therapy for clinical use. The adoptive transfer of engineered autologous T cells, such as chimeric antigen receptor (CAR) T cells, has been remarkably successful in patients with leukemia and lymphoma with cluster of differentiation (CD)19 expression. Because of the higher number of antigen choices and reduced incidence of cytokine release syndrome (CRS) than CAR-T cells, T cell receptor (TCR)-T cells are also considered a promising immunotherapy. More therapeutic targets for other cancers need to be explored due to the human leukocyte antigen (HLA)-restricted recognition of TCR-T. Major histocompatibility complex (MHC), class I-related (MR1)-restricted T cells can recognize metabolites presented by MR1 in the context of host cells infected with pathogens. MR1 is expressed by all types of human cells. Recent studies have shown that one clone of a MR1-restricted T (MR1-T) cell can recognize many types of cancer cells without HLA-restriction. These studies provide additional information on MR1-T cells for cancer immunotherapy. This review describes the complexity of MR1-T cell TCR in diseases and the future of cancer immunotherapy.

Fibroblast growth factor receptor 4 (FGFR4) is a cell surface receptor tyrosine kinases (RTKs) for FGFs. Several studies have focused on the association between FGFR4 polymorphisms and cancer development. This meta-analysis aimed to estimate the association between FGFR4 rs351855 (Gly 388 Arg), rs1966265 (Val 10 Ile), rs7708357, rs2011077, and rs376618 polymorphisms and cancer risk. Eligible studies were identified from electronic databases. All statistical analyses were achieved with the STATA 14.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantitatively estimate the association. Overall, no significant association was found among rs351855, rs2011077, and rs376618 polymorphisms with the risk of overall cancer. The rs1966265 polymorphism significantly decreased the risk of cancer in recessive (OR = 0.87, 95% CI = 0.78–0.97, P =0.009, TT vs CT+CC) genetic model. Whereas the rs7708357 polymorphism was positively associated with cancer risk in dominant (OR = 1.17, 95% CI = 1.02–1.36, P =0.028) genetic model. Stratified analysis revealed that rs351855 variant significantly increased the risk of prostate cancer in heterozygous (OR = 1.16, 95% CI = 1.02–1.32, P =0.025 AG vs GG), dominant (OR = 1.20, 95% CI = 1.06–1.35, P =0.004, AG+AA vs GG), and allele (OR = 1.22, 95% CI = 1.06–1.41, P =0.005, A vs G) genetic models. In summary, the findings of this meta-analysis indicate that rs1966265, rs7708357, and rs351855 polymorphisms are correlated to cancer development. Further well-designed studies are necessary to draw more precise conclusions.

Background: Previously published studies have indicated that lymphoid enhancer-binding factor 1 (LEF1) expression could be recognized as a valuable biomarker to evaluate clinical outcome for various types of malignant cancer, but the results remained controversial. Therefore, we conducted this meta-analysis to pool the published estimates and discuss the relationship of LEF1 expression with cancer prognosis. Methods: Five electronic databases Pubmed, Web of Science, Embase, CNKI, and Wanfang were systematically searched for eligible literatures. Hazard ratios (HRs) and 95% confidence intervals (CIs) from the included studies were combined to estimate the effect of LEF1 expression on cancer patients’ survival. Results: Eleven original studies met the criteria and were enrolled for analysis. The results indicated that compared with patients in low LEF1 expression group, patients in high LEF1 expression group tended to have shorter overall survival (HR = 1.74, 95% CI: 1.06–2.86, P =0.029), especially for patients with solid tumors (HR = 2.39, 95% CI: 1.86–3.08, P =0.000). Conclusions: Individual evidence about the prognostic value of LEF1 expression in human cancers was limited. Our meta-analysis supported the suggestion that elevated LEF1 expression could function as a promising biomarker to predict the clinical outcomes for malignant cancers, especially solid tumors. More high-quality clinical studies are warranted to highlight the prognostic value of LEF1 expression in human cancers.

Background: SNHG15 has been reported to be aberrantly expressed in various tumor tissues and could serve as a promising prognostic cancer biomarker. Previous studies on SNHG15 yielded inconsistent results with insufficient sampling. Here, a meta-analysis was conducted to investigate the prognostic value of SNHG15 in multiple cancers. Methods: Relevant studies were retrieved from six electronic databases including PubMed, Cochrane Library, Google Scholar, Embase, Web of Science and China National Knowledge Infrastructure (CNKI). Fifteen publications comprising 1318 patients were included. The publication bias was identified by the Begg’s Test, and the sensitivity analysis was also performed. Results: The results demonstrated a positive correlation between high expression level of lncSNHG15 and short overall survival (hazard ratio (HR) = 2.07, 95% confidence interval (CI), 1.48–2.88; P <0.0001) and disease-free survival (DFS) (HR = 2.32, 95% CI, 1.53–3.53; P <0.0001). The analysis based on different cancer types showed that SNHG15 had the most prominent prognostic potential in Glioma (HR = 3.81; 95% CI, 0.84–42.69; P =0.28). Moreover, the high expression level of lnc SNHG15 indicated advanced TNM stage (OR = 2.52; 95% CI, 1.33–4.76; P =0.00001), lymph node metastasis (OR = 2.41, 95% CI, 0.99–4.81; P =0.05), bigger tumor size (OR = 2.06; 95% CI, 1.03–4.13; P =0.04) and poor histological grade (OR = 2.62, 95% CI, 1.90–3.59; P <0.00001), yet no association with distant metastasis (OR = 1.64, 95% CI, 0.40–6.74; P =0.49), age (OR = 0.98, 95% CI, 0.78–1.22; P =0.84) and gender (OR = 0.9, 95% CI, 0.71–1.14; P =0.3838) was found. Its conclusions further confirmed by exploring TCGA databases. Conclusion: It revealed that lnc SNHG15 might be a promising prognostic biomarker of multiple cancer types, especially in Glioma.

There is still no conclusion on the potential effect of the rs2295080 and rs2536 polymorphisms of mTOR (mammalian target of rapamycin) gene on different cancers. Herein, we performed a comprehensive assessment using pooled analysis, FPRP (false-positive report probability), TSA (trial sequential analysis), and eQTL (expression quantitative trait loci) analysis. Eighteen high-quality articles from China were enrolled. The pooled analysis of rs2295080 with 9502 cases and 10,965 controls showed a decreased risk of urinary system tumors and specific prostate cancers [TG vs. TT, TG+GG vs. TT and G vs. T; P <0.05, OR (odds ratio) <1]. FPRP and TSA data further confirmed these results. There was an increased risk of leukemia [G vs. T, GG vs. TT, and GG vs. TT+TG genotypes; P <0.05, OR>1]. The eQTL data showed a potential correlation between the rs2295080 and mTOR expression in whole blood samples. Nevertheless, FPRP and TSA data suggested that more evidence is required to confirm the potential role of rs2295080 in leukemia risk. The pooled analysis of rs2536 (6653 cases and 7025 controls) showed a significant association in the subgroup of “population-based” control source via the allele, heterozygote, dominant, and carrier comparisons ( P <0.05, OR>1). In conclusion, the TG genotype of mTOR rs2295080 may be linked to reduced susceptibility to urinary system tumors or specific prostate cancers in Chinese patients. The currently data do not strongly support a role of rs2295080 in leukemia susceptibility. Large sample sizes are needed to confirm the potential role of rs2536 in more types of cancer.

Background: The evidence for an association between the adiponectin gene (ADIPOQ) polymorphism rs182052 and cancer risk is inconsistent. We performed a meta-analysis to obtain more precise conclusions. Methods: The PubMed, Embase, and Web of Science databases were searched until July 11, 2019. And seven epidemiology studies were retrieved, including 4,929 cases and 5,625 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Results: The meta-analysis demonstrated that rs182052 significantly increased the risk of cancer under the allele, homozygote, dominant, and recessive models, based on an overall analysis (A vs. G: OR, 1.09, 95% CI, 1.03–1.15, P =0.003; AA vs. GG: OR, 1.20, 95% CI, 1.07–1.34, P =0.002; AA+GA vs. GG: OR, 1.12, 95% CI, 1.03–1.22, P =0.010; AA vs. GA+GG: OR, 1.12, 95% CI, 1.01–1.23, P =0.025). In the stratified analysis by ethnicity, rs182052 significantly increased the cancer risk in both Asian and Caucasian populations under one or several genetic models. In the stratified analysis by cancer type, rs182052 significantly increased the risk of renal cell carcinoma (RCC) under the five models. Conclusions: Meta-analysis based on present studies suggests that rs182052 can increase the cancer risk.

Lipid synthesis is the recently found metabolism of cancer cells after their metastasis to lymph nodes (LNs). Carbonic acid is the main byproduct of the lipid metabolism in such cells which resulted in acidification of LN ambient. Hence, calibrated pH sensing could be a diagnostic method to find involved LNs. Here, we designed a simple pH sensing method by a syringe containing sterile PBS and embedded by litmus paper to intraoperatively check the pH of LN fluid. Injected phosphate buffer saline (PBS) would homogenize the LN fluid and litmus needle would detect the pH of the LN. We presented an experimental pathological calibration for the pH values in correlation with cancerous states of the LNs. This system named metabolism based metastatic lymph diagnoser (MMLD) could be a real-time noninvasive tool for precise and fast diagnosis of involved LNs.

Purpose: To provide a comprehensive account of the association of five Lymphotoxin-α ( LTA ) gene polymorphisms (rs1041981, rs2229094, rs2239704, rs746868, rs909253) with susceptibility to cancer. Methods: A literature search for eligible candidate gene studies published before 28 February 2020 was conducted in the PubMed, Medline, Google Scholar and Web of Science. The following combinations of main keywords were used: (LTA OR Lymphotoxin alpha OR TNF-β OR tumor necrosis factor-beta) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (cancer OR tumor OR neoplasm OR malignancy OR carcinoma OR adenocarcinoma). Potential sources of heterogeneity were sought out via subgroup and sensitivity analysis, and publication bias were estimated. Results: Overall, a total of 24 articles with 24577 cases and 33351 controls for five polymorphisms of LTA gene were enrolled. We identified that rs2239704 was associated with a reduced risk of cancer. While for other polymorphisms, the results showed no significant association with cancer risk. In the stratified analysis of rs1041981, we found that Asians might have less susceptibility to cancer. At the same time, we found that rs2239704 was negatively correlated with non-Hodgkin lymphoma (NHL). While, for rs909253, an increased risk of cancer for Caucasians and HCC susceptibility were uncovered in the stratified analysis of by ethnicity and cancer type. Conclusion: LTA rs2239704 polymorphism is inversely associated with the risk of cancer. LTA rs1041981 polymorphism is negatively associated with cancer risk in Asia. While, LTA rs909253 polymorphism is a risk factor for HCC in Caucasian population.

The processes that lead to lung adenocarcinoma (LUAD) metastasis are poorly characterized. Spindle and kinetochore associated complex subunit 3 (SKA3) plays a key role in cervical cancer development, but its contribution to LUAD is unknown. Here, we found that SKA3 is overexpressed in LUAD and its expression correlates with lymph node metastasis and poor prognosis. SKA3 silencing experiments identified SKA3 as an oncogene that promotes the metastasis of LUAD cell lines and tissues. SKA3 was found to induce the expression of matrix metalloproteinase (MMP)-2, -7, and -9, which activate PI3K–AKT. SKA3 was also found to bind and activate EGFR to activate PI3K–AKT. In summary, we identify a role for SKA3 in LUAD metastasis through its ability to bind EFGR and activate PI3K–AKT signaling.

Background: Oxycodone is an opioid medication used for the treatment of pain in cancer patients. However, little is known on the direct effects of oxycodone on cancer cells. Aim: To determine the effects and mechanisms of oxycodone in cancer cells. Materials and Methods: Proliferation, survival and migration assays were performed on multiple types of cancer cells. Epithelial growth factor receptor (EGFR)/ERK/Akt pathway and oxidative stress were investigated after oxycodone treatment. Results: Oxycodone can either stimulate growth and migration without affecting survival in MDA-468 cells or inhibit growth and survival without affecting migration in SKBR3 and Caco2 cells. In addition, oxycodone can either attenuate or stimulate efficacy of chemotherapeutic drugs in cancer, depending on the type of cancer cells and nature of action of oxycodone as single drug alone. Our mechanism studies suggest that the stimulatory and inhibitory effects of oxycodone are associated with EGFR expression levels in cancer cells. In cancer cells with high EGFR level, oxycodone activates EGFR signaling in cancer cells, leading to stimulatory effects in multiple biological activities, and this is dependent on opioid receptor. In cancer cells with low EGFR level, oxycodone induces mitochondria-mediated caspase activity and oxidative stress and damage, leading to cell death. Conclusions: Our work is the first to demonstrate systematic analysis of oxycodone’s effects and mechanism of action in cancer. The activation of EGFR signaling by oxycodone may provide a new guide in the clinical use of oxycodone, in particular for cancer patients with high EGFR levels.

Background: Previous case–control studies have suggested that apurinic/apyrimidinic endonuclease 1 ( APE1 ) rs1760944 T>G polymorphism may be associated with cancer risk. Here, we carried out an updated meta-analysis to focus on the correlation between APE1 rs1760944 T>G locus and the risk of cancer. Methods: We used the crude odds ratios (ORs) with their 95% confidence intervals (CIs) to evaluate the possible relationship between the APE1 rs1760944 T>G polymorphism and cancer risk. Heterogeneity, publication bias and sensitivity analysis were also harnessed to check the potential bias of the present study. Results: Twenty-three independent studies involving 10166 cancer cases and 11598 controls were eligible for this pooled analysis. We found that APE1 rs1760944 T>G polymorphism decreased the risk of cancer in four genetic models (G vs. T: OR, 0.87; 95% CI, 0.83–0.92; P <0.001; GG vs. TT: OR, 0.77; 95% CI, 0.69–0.86; P <0.001; GG/TG vs. TT: OR, 0.83; 95% CI, 0.77–0.89, P <0.001 and GG vs. TT/TG: OR, 0.85; 95% CI, 0.80–0.92, P <0.001). Results of subgroup analyses also demonstrated that this single-nucleotide polymorphism (SNP) modified the risk among lung cancer, breast cancer, osteosarcoma, and Asians. Evidence of publication bias was found in the present study. When we treated the publication bias with ‘trim-and-fill’ method, the adjusted ORs and CIs were not significantly changed. Conclusion: In conclusion, current evidence highlights that the APE1 rs1760944 T>G polymorphism is a protective factor for cancer susceptibility. In the future, case–control studies with detailed risk factors are needed to confirm or refute our findings.

Objectives In the present study, we examined available articles from online databases to comprehensively investigate the effect of the XPC (xeroderma pigmentosum complementation group C) rs2228000 polymorphism on the risk of different types of clinical cancer. Methods We conducted a group of overall and subgroup pooling analyses after retrieving the data from four databases (updated till September 2019). The P -value of association, OR (odds ratios), and 95% CI (confidence interval) were calculated. Results We selected a total of 71 eligible studies with 26835 cancer cases and 37069 controls from the 1186 retrieved articles. There is an enhanced susceptibility for bladder cancer cases under T vs. C [ P =0.004; OR (95% CI) = 1.25 (1.07, 1.45)], TT vs. CC [ P =0.001; 1.68 (1.25, 2.26)], CT+TT vs. CC [ P =0.016; 1.26 (1.04, 1.53)], and TT vs. CC+ CT [ P =0.001; 1.49 (1.18, 1.90)] compared with negative controls. Additionally, there is an increased risk of breast cancer under T vs. C, TT vs. CC and TT vs. CC+ CT ( P <0.05, OR > 1). Nevertheless, there is a decreased risk of gastric cancer cases in China under T vs. C [ P =0.020; 0.92 (0.85, 0.99)], CT vs. CC [ P =0.001, 0.83 (0.73, 0.93)], and CT+TT vs. CC [ P =0.003, 0.84 (0.76, 0.94)]. Conclusions The TT genotype of XPC rs2228000 may be linked to an increased risk of bladder and breast cancer, whereas the CT genotype is likely to be associated with reduced susceptibility to gastric cancer in the Chinese population.

Cancer incidence rate has increased so much that it is the second leading cause of deaths worldwide after cardiovascular diseases. Sensitive and specific biomarkers are needed for an early diagnosis of cancer and in-time treatment. Recent studies have found that long non-coding RNAs (lncRNAs) participate in cancer tumorigenesis. LncRNA P73 antisense RNA 1T (TP73-AS1), also known as KIAA0495 and p53-dependent apoptosis modulator (PDAM), is located in human chromosomal band 1p36.32 and plays a crucial role in many different carcinomas. This review summarizes current findings on the role of TP73-AS1 and its signaling pathways in various cancers, including glioma, esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), osteosarcoma, gastric cancer (GC), clear cell renal cell carcinoma (ccRCC), breast cancer (BC), bladder cancer, ovarian cancer, cholangiocarcinoma (CCA), lung cancer, and pancreatic cancer. Its aberrant expression generally correlates with clinicopathological characterization of patients. Moreover, TP73-AS1 regulates proliferation, migration, invasion, apoptosis, and chemoresistance cancer mechanisms, both in vivo and in vitro , through different signaling pathways. Therefore, TP73-AS1 may be considered as a marker for diagnosis and prognosis, also as a target for cancer treatment.

Background: Dysregulated expression of long non-coding RNA gastric carcinoma high expressed transcript 1 (lncRNA GHET1) has been observed in several cancers, however, definite conclusion on the prognostic value of lncRNA GHET1 expression in human cancers has not been determined. The aim of this meta-analysis was to evaluate the prognostic significance of lncRNA GHET1 expression in cancers. Methods: PubMed, Web of Science and Embase were comprehensively searched for relevant studies. Meta-analyses of overall survival (OS) and clinicopathological features were conducted. Results: Ten studies were finally analyzed in the present study. High lncRNA GHET1 expression was associated with shorter OS than low lncRNA GHET1 expression in cancers (hazard ratio (HR) = 2.59, 95% CI = 1.93–3.47, P <0.01). Online cross-validation using The Cancer Genome Atlas (TCGA) data observed similar results (HR = 1.10, P <0.05). When compared with low lncRNA GHET1 expression, high lncRNA GHET1 expression was related to larger tumor size ( P <0.01), worse differentiation ( P <0.01), earlier distant metastasis ( P =0.02), earlier lymph node metastasis ( P <0.01) and more advanced clinical stage ( P <0.01). Conclusion : High lncRNA GHET1 expression is associated with worse cancer prognosis and can serve as a promising prognostic factor of human cancers.

Patients with spinal cord injury (SCI) have an increased risk of developing esophageal, bladder and hematologic malignancies compared with the normal population. In the present study, we aimed to identify, through in silico analysis, miRNAs and their target genes related to the three most frequent types of cancer in individuals with SCI. In a previous study, we reported a pattern of expression of miRNAs in 17 sedentary SCI males compared with 22 healthy able-bodied males by TaqMan OpenArray. This list of miRNAs deregulated in SCI patients was uploaded to miRWALK2.0 to predict the target genes and pathways of selected miRNAs. We used Cytoscape software to construct the network displaying the miRNAs and their gene targets. Among the down-regulated miRNAs in SCI, 21, 19 and 20 miRNAs were potentially associated with hematological, bladder and esophageal cancer, respectively, and three target genes ( TP53, CCND1 and KRAS ) were common to all three types of cancer. The three up-regulated miRNAs were potentially targeted by 18, 15 and 10 genes associated with all three types of cancer. Our current bioinformatics analysis suggests the potential influence of several miRNAs on the development of cancer in SCI. In general, these data may provide novel information regarding potential molecular mechanisms involved in the development of cancer among individuals with SCI. Further studies aiming at understanding how miRNAs contribute to the development of the major cancers that affect patients after SCI may help elucidate the role of these molecules in the pathophysiology of the disease.

Radiotherapy is one of the main modalities of cancer treatment. However, tumor recurrence following radiotherapy occurs in many cancer patients. A key to solving this problem is the optimization of radiosensitivity. In recent years, long non-coding RNAs (lncRNAs), which affect the occurrence and development of tumors through a variety of mechanisms, have become a popular research topic. LncRNAs have been found to influence radiosensitivity by regulating various mechanisms, including DNA damage repair, cell cycle arrest, apoptosis, cancer stem cells regulation, epithelial–mesenchymal transition, and autophagy. LncRNAs are expected to become a potential therapeutic target for radiotherapy in the future. This article reviews recent advances in the role and mechanism of lncRNAs in tumor radiosensitivity.

Piles of evidence have supported the relationship between miR-618 rs2682818 polymorphism and tumorigenesis, but the conclusion remains inconsistent. In the present study, we conducted a meta-analysis to sniff out the potential risk between miR-618 rs2682818 and overall cancers. Crude odds ratios (ORs) and 95% confidence intervals (CIs) analyzed by Z -test were employed to estimate the potential interrelation in five genetic models. We also prospected how the rs2682818 affects the second structure of miR-618. Finally, 10 independent studies meet the enrolled criteria, along with 4099 cancer cases and 5057 healthy controls. Overall, no exceeding interrelation was sniffed out in the pooled data among five inherited models, as well as stratified analyses. Whereas, the enhanced cancer risk of miR-618 rs2682818 variant stratified by breast cancer was revealed, in heterozygote genetic model (AC vs. CC: OR = 1.291, 95%CI = 1.012–1.648, P = 0.040) and dominant contrast model (AA + AC vs. CC: OR = 1.280, 95%CI = 1.009–1.623, P = 0.042). The second structure prediction result shown that the mutant A allele might change the first stem-loop of miR-618, and the free energy of it would turn from –39.1 to –35.1 kcal/mol. All in all, our meta-analysis had successfully chased down that miR-618 rs2682818 polymorphism is not linked with overall cancer risk, but in the dominant genotype of breast cancer.

Leptin receptor (LEPR) signaling may be involved in promoting angiogenesis and proliferation, inhibiting apoptosis and playing a vital role in the progression of carcinogenesis. A number of studies have focused on the association of LEPR rs1137101 variants with susceptibility of cancer, however, the observed results were controversial. We searched literature on the relationship of LEPR rs1137101 G>A polymorphism with cancer risk by using PubMed and Embase databases, covering all publications up to 14 October 2018. In total, 44 case–control studies with 35,936 subjects were included. After combining all eligible studies, we identified null relationship between LEPR gene rs1137101 G>A polymorphism and overall cancer risk [A vs. G: odds ratio (OR ) = 0.97, 95% confidence interval (CI ) = 0.89–1.06, P = 0.547; AA vs. GG: OR = 0.93, 95% CI = 0.78–1.13, P = 0.476; AA/GA vs. GG: OR = 0.99, 95% CI = 0.91–1.09, P = 0.890 and AA vs. GA/GG: OR = 0.92, 95% CI = 0.82–1.04, P = 0.198]. However, in a subgroup analysis, there was an increased susceptibility of oral and oropharyngeal cancer in AA vs. GA/GG genetic model (OR, 1.83; 95% CI, 1.01–3.33; P =0.048). Considering the limited participants were included, the findings might be underpowered. Sensitivity analysis identified that any independent study omitted did not materially influence the pooled ORs and CIs. The results of publication bias detection showed that there was no evidence of bias. In summary, this analysis indicates that no significant association of cancer risk was identified to be correlated with rs1137101 G>A variants, even in stratified analyses.

Rs189037 (G>A) is an important functional variant with ataxia telangiectasia mutated ( ATM ) gene, which might affect ATM ’s expression involvement in several human cancers. Increasing evidence reveals that smoking-related cancers have distinct molecular characteristics from non-smoking cancers. Until now, the role of ATM rs189037 in cancer risk stratified by smoking status still remains unclear. To evaluate the association between ATM rs189037 and cancer risk based on smoking status, we performed this meta-analysis by a comprehensive literature search via databases of PubMed, Embase, Web of Science and CNKI, updated till January 2019. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were extracted from eligible studies if available, to assess the relationship strengths. A total of seven eligible studies were included, comprising 4294 cancer patients (smokers: 1744 [40.6%]) and 4259 controls (smokers: 1418 [33.3%]). Results indicated a significant association of ATM rs189037 with cancer risk. In non-smokers, compared with GG genotype, AA genotype increased a 1.40-fold risk of overall cancer (OR = 1.40, 95% CI = 1.15–1.70, P heterogeneity =0.433, I 2 = 0.0%). Subgroup analysis in lung cancer (LC) also exhibited a significant result (OR = 1.41, 95% CI = 1.15–1.73, P heterogeneity =0.306, I 2 = 17.0%) only in non-smokers. However, the association was not observed in smokers, no matter for overall cancer or for LC. Our findings highlight that ATM rs189037 significantly increases cancer susceptibility in non-smokers, rather than in smokers. The association is prominent in LC.

Long non-coding RNA (lncRNA) FEZF1 antisense RNA 1 (FEZF1-AS1) has been shown to be up-regulated in tumor tissues and cells, and exerts oncogenic effects on various types of malignancies. However, the expression and function of FEZF1-AS1 was still fully unclear in retinoblastoma. The purpose of our study was to investigate the expression and clinical value of FEZF1-AS1 in retinoblastoma patients, and explore the effect of FEZF1-AS1 on retinoblastoma cell proliferation, migration and invasion. In our results, levels of FEZF1-AS1 expression were elevated in retinoblastoma tissue specimens and cell lines compared with adjacent normal retina tissue specimens and human retinal pigment epithelial cell line, respectively. The correlation analysis indicated that high FEZF1-AS1 expression was significantly correlated with present choroidal invasion and optic nerve invasion. Survival analysis suggested that retinoblastoma patients in high FEZF1-AS1 expression group had obviously short disease-free survival (DFS) compared with retinoblastoma patients in low FEZF1-AS1 expression group, and high FEZF1-AS1 expression was an independent unfavorable prognostic factor for DFS in retinoblastoma patients. Loss-of-function study indicated silencing FEZF1-AS1 expression inhibited retinoblastoma cell proliferation, invasion and migration. In conclusion, FEZF1-AS1 functions as an oncogenic lncRNA in retinoblastoma.

Association between the xeroderma pigmentosum complementation group F (XPF)rs2276466 located in the excision repair cross complementation group 4 (ERCC4) gene and cancer susceptibility has been widely investigated. However, results thus far have remained controversial. A meta-analysis was performed to identify the impact of this polymorphism on cancer susceptibility. PubMed, Embase and Science-Web databases were searched systematically up to May 20, 2018, to obtain all the records evaluating the association between the rs2276466 polymorphism and the risk of all types of cancers. We used the odds ratio (OR) as a measure of effect, and pooled the data in a Mantel-Haenszel weighed random-effects meta-analysis to provide a summary estimate of the impact of this polymorphism on gastrointestinal cancer, neurogenic cancer and other cancers (breast cancer and SCCHN). All the analyses were carried out in STATA 14.1.11 case–control studies that consisted of 5730 cases and 6756 controls, were eventually included in our meta-analysis. The significant association was observed between the XPFrs2276466 polymorphism and neurogenic cancer susceptibility (recessive model: OR = 1.648, 95% CI = 1.294–2.098, P <0.001). Furthermore, no significant impact of this polymorphism was detected on decreased gastrointestinal cancer risk (dominant model: OR = 1.064, 95%CI = 0.961–1.177, P = 0.233). The rs2276466 polymorphism might play different roles in carcinogenesis of various cancer types. Current evidence did not suggest that this polymorphism was directly associated with gastrointestinal susceptibility. However, this polymorphism might contribute to increased neurogenic cancer risk. More preclinical and epidemiological studies are still imperative for further evaluation

MiR-19a was aberrantly expressed in various types of cancers and was observed to be potentially associated with the prognosis of cancer patients. The present analysis aims to elucidate its precise predictive value in various human malignancies. Online electronic searches of PubMed, Web of Science (WOS), Embase in English and VIP, Wanfang, SinoMed, and the China National Knowledge Infrastructure (CNKI) in Chinese up to September 8, 2018 were conducted. As a result, in overall analysis, a significant association was identified between miR-19a levels and OS (HRs = 2.31, CI: 1.11–4.83). The relation of miR-19a expression to OS was further recognized by fixed model within the studies of sample size less than 150 (HRs = 1.68, CI: 1.35–2.08), NOS scores greater than or equal to 8 (HRs = 1.53, CI: 1.13–2.06) or less than 8 (HRs = 1.89, CI: 1.58–2.27), specimen derived from tumor (HRs = 1.73, CI: 1.42–2.12) or blood (HRs = 1.87, CI: 1.46–2.40) and the patients of osteosarcoma (HRs = 7.17, CI: 5.04–10.21). Sensitivity analyses revealed no significant results. The association between miR-19a expression level and DFS was also found to be significant (HRs = 2.03, CI: 1.13–3.66). Correlations between miR-19a levels and clinicopathological features were examined and revealed that lymph node metastasis was significantly associated with miR-19a expression levels (OR = 0.565, CI: 0.346–0.921). Summarily, the over expression of miR-19a was an underlying risk of poor prognosis in many human malignancies, especially in osteosarcoma. Moreover, elevated miR-19a expression was linked to the potential of lymph node metastasis.

Ten-eleven translocation (TET) proteins are abnormally expressed in various cancers. Osteosarcoma cells were treated with hydroxyurea to investigate the expression pattern of TET proteins in these cells. The expression of TET1 was increased in U2OS cells after treatment with hydroxyurea. In addition, hydroxyurea increased cell apoptosis and altered the cell cycle. TET proteins catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC); therefore, 5mC and 5hmC levels were evaluated. Increased 5hmC levels were observed after the hydroxyurea treatment. Experiments examining cell apoptosis and the cell cycle after knockdown and overexpression of TET1 were conducted to further investigate whether TET1 expression affected cell growth. The overexpression of TET1 increased cell apoptosis and inhibited cell growth. Taken together, TET1 expression regulated proliferation and apoptosis in U2OS cells, changes that were associated with 5hmC levels.

Human leucocyte antigen-G (HLA-G) plays an important role in the progression of human cancers. A growing number of published studies have investigated the correlation between the HLA-G 3′ untranslated region (3′UTR) 14-bp insertion/deletion ( Ins/Del ) polymorphism and the associated cancer risk in different populations. However, results from previous studies are inconclusive and inconsistent for the different type of cancers. Therefore, we undertook a meta-analysis to assess the effects of the HLA-G 14-bp Ins/Del polymorphism on cancer risk. A systematic literature search was conducted in PubMed, Web of Science, CNKI, VIP, and Wanfang databases to obtain relevant studies up to 28 January 2019. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used. Twenty-five published case–control studies comprising 4981 cases and 6391 controls were included in the current meta-analysis. The results of the overall analysis revealed that the HLA–G 14–bp Ins/Ins genotype and Ins allele were associated with the total cancer risk in the homozygote comparison model ( Ins/Ins vs. Del/Del : OR = 0.80, CI = 0.64–1.00; P =0.049) and the allelic comparison model ( Ins vs. Del : OR = 0.89, CI = 0.81–0.99; P =0.035), with a protective role. Further subgroup analyses indicated that the HLA–G 14–bp Ins/Del polymorphism was associated with the risk of breast cancer and oesophageal cancer (EC), and significant risk of cancer was also observed in Mixed populations and population-based (PB). The results of our meta-analysis show that the HLA–G 14-bp Ins/Del polymorphism plays an important role in cancer risk, particularly in breast cancer and esophageal cancer in Mixed populations. Additional case–control studies with different types of cancer spanning different ethnicities are needed to extend the present findings.

Background: Urothelial carcinoma associated 1 (UCA1), a novel long noncoding RNA (lncRNA) which is first discovered in 2006 in human bladder cancer and has become a hot spot in recent years. UCA1 has been demonstrated correlated with clinical outcomes in various cancers. However, the results from each study are insufficient and not completely consistent. Therefore, we perform a systematic meta-analysis to evaluate the value for a feasible biomarker for metastasis and prognosis of cancer. Methods: Relevant English literatures were searched in PubMed, Cochrane Library, Web of science, Embase databases and Chinese literatures were searched in Chinese National Knowledge Infrastructure Wanfang from inception up to 17 April 2018. The pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) using random/fixed-effect were used to identify the relationship between UCA1 and lymph node metastasis (LNM) or overall survival (OS) of cancer patients. Subgroup analysis and sensitivity analysis were performed. The current meta-analysis was performed using Review Manager 5.3 and Stata 12.0 software. Results: A total of 3411 patients from 38 studies were finally included. Patients who with high UCA1 expression suffered from an increased risk of LNM (OR = 2.50; 95% CI: 1.93–3.25). UCA1 was also significantly associated with OS (HR = 2.05; 95% CI: 1.77–2.38). Subgroup analyses across several different variables also showed the similar results in LNM and OS of cancer patients. Conclusion: High expression of UCA1 was linked with poor clinical outcome. UCA1 can serve as a potential molecular marker for metastasis and prognosis in different types of cancers.

Innate immunity comprises several inflammation-related modulatory pathways which receive signals from an array of membrane-bound and cytoplasmic pattern recognition receptors (PRRs). The NLRs (NACHT (NAIP (neuronal apoptosis inhibitor protein), C2TA (MHC class 2 transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TP1 (telomerase-associated protein) and Leucine-Rich Repeat (LRR) domain containing proteins) relate to a large family of cytosolic innate receptors, involved in detection of intracellular pathogens and endogenous byproducts of tissue injury. These receptors may recognize pathogen-associated molecular patterns (PAMPs) and/or danger-associated molecular patterns (DAMPs), activating host responses against pathogen infection and cellular stress. NLR-driven downstream signals trigger a number of signaling circuitries, which may either initiate the formation of inflammasomes and/or activate nuclear factor κB (NF-κB), stress kinases, interferon response factors (IRFs), inflammatory caspases and autophagy. Disruption of those signals may lead to a number of pro-inflammatory conditions, eventually promoting the onset of human malignancies. In this review, we describe the structures and functions of the most well-defined NLR proteins and highlight their association and biological impact on a diverse number of cancers.

Alcohol consumption has been established to be a major factor in the development and progress of cancer. Genetic polymorphisms of alcohol-metabolism genes result in differences between individuals in exposure to acetaldehyde, leading to possible carcinogenic effects. Arg47His (rs1229984 G > A) in ADH1B have been frequently studied for its potential effect on carcinogenesis. However, the findings are as yet inconclusive. To gain a more precise estimate of this potential association, we conducted a meta-analysis including 66 studies from 64 articles with 31999 cases and 50964 controls. The pooled results indicated that ADH1B Arg47His polymorphism is significantly associated with the decreased risk of overall cancer (homozygous model, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.49–0.77; heterozygous model, OR = 0.71, 95% CI = 0.60–0.84; recessive model, OR = 0.83, 95% CI = 0.76–0.91; dominant model, OR = 0.62, 95% CI = 0.53–0.72; and allele comparison, OR = 0.82, 95% CI = 0.75–0.89). Stratified analysis by cancer type and ethnicity showed that a decreased risk was associated with esophageal cancer and head and neck cancer amongst Asians. In conclusion, our meta-analysis suggested that ADH1B Arg47His polymorphism was significantly associated with decreased overall cancer risk. These findings need further validation in large multicenter investigations.

LINC00599 has been suggested to be involved in physiological and pathological processes including carcinogenesis. However, the clinical and prognostic significance of LINC00599 in glioma patients and the effect of LINC00599 on glioma cell migration and invasion remain unknown. In our results, we first observe the expression of LINC00599 in 31 types of human cancers including tumor tissues and corresponding normal tissues at The Cancer Genome Atlas (TCGA) database, and found that LINC00599 expression levels were only reduced in lower grade glioma (LGG) tissues and glioblastoma multiforme (GBM) tissues compared with normal brain tissues. Moreover, we confirmed levels of LINC00599 expression were decreased in glioma tissues and cell lines compared with matched adjacent normal tissues and normal human astrocytes (NHAs), respectively. Meanwhile, we found that glioma tissues with WHO III-IV grade exhibited lower levels of LINC00599 expression than glioma tissues with I-II grade. The survival analysis at TCGA data showed low LINC00599 expression was associated with poor disease-free survival and overall survival in glioma patients. In vitro study suggested up-regulation of LINC00599 depressed glioma cell migration and invasion through regulating epithelial–mesenchymal transition (EMT) process. In conclusion, LINC00599 acts as a tumor-suppressing long non-coding RNA (lncRNA) in glioma.

Background : Several studies demonstrated that long non-coding RNA differentiation antagonizing non-protein coding RNA (lncRNA DANCR) expression might have the potential capacity to predict the cancer prognosis, however, definite conclusion has not been obtained. The aim of this meta-analysis was to evaluate the prognostic value of lncRNA DANCR expression in cancers. Methods : PubMed, Web of Science, Scopus and Embase were comprehensively searched for relevant studies. Studies meeting all inclusion standards were included into this meta-analysis. The analysis of overall survival (OS), disease-free survival (DFS) or clinicopathological features was conducted. Results : Eleven studies containing 1,154 cancer patients were analyzed in this meta-analysis. The results showed, compared with low lncRNA DANCR expression, high lncRNA DANCR expression was significantly associated with shorter OS (HR=1.85, 95%CI=1.52-2.26, P&lt;0.01) and DFS (HR=1.82, 95%=1.43-2.32, P&lt;0.01) in cancers. Besides, high lncRNA DANCR expression predicted deeper tumor invasion (P&lt;0.01), earlier lymph node metastasis (P&lt;0.01), earlier distant metastasis (P&lt;0.01) and more advanced clinical stage (P&lt;0.01) compared with low lncRNA DANCR expression in cancer populations. Conclusion : High lncRNA DANCR expression was associated with worse prognosis compared with low lncRNA DANCR expression in cancers. LncRNA DANCR expression could serve as a prognostic factor of human cancers.

The role of forkhead box P3 (FOXP3) protein in tumorigenesis has long been controversial and existing data on the association between FOXP3 gene polymorphisms and cancer susceptibility were inconsistent. Here, we conducted a meta-analysis to better clarify the relationship. A comprehensive search of studies published from July 2008 to June 2018 was conducted. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were performed using the Revman 5.2 software. A total of 12 articles with 19 case–control studies and 10389 participants were included. Three FOXP3 polymorphisms and six cancer types were evaluated. While no significant results were observed in overall and breast cancer groups for rs3761548 (A/C) polymorphisms, the pooled data showed an elevated risk of cancer in variant AA genotypes and A allele for Chinese population (AA vs. AC+CC: OR = 1.61, 95% CI = 1.09, 2.39; AA vs. CC: OR = 1.74, 95% CI = 1.05, 2.89; A vs. C: OR = 1.34, 95% CI = 1.00, 1.78). Neither the overall group analyses nor the subgroup analyses stratified by cancer type and ethnicity proposed any significant association of rs2280883 (C/T) and rs3761549 (T/C) polymorphisms with cancer susceptibility. This meta-analysis suggested that FOXP3 rs3761548 (A/C) polymorphisms were associated with increased cancer risk in Chinese population while rs2280883 (C/T) and rs3761549 (T/C) polymorphisms were not. More large-sample researches with diverse ethnicities and cancer types are needed to draw a concrete conclusion.

The Activator Protein 2 (AP-2) transcription factor (TF) family is vital for the regulation of gene expression during early development as well as carcinogenesis process. The review focusses on the AP-2α and AP-2γ proteins and their dualistic regulation of gene expression in the process of carcinogenesis. Both AP-2α and AP-2γ influence a wide range of physiological or pathological processes by regulating different pathways and interacting with diverse molecules, i.e. other proteins, long non-coding RNAs (lncRNA) or miRNAs. This review summarizes the newest information about the biology of two, AP-2α and AP-2γ, TFs in the carcinogenesis process. We emphasize that these two proteins could have either oncogenic or suppressive characteristics depending on the type of cancer tissue or their interaction with specific molecules. They have also been found to contribute to resistance and sensitivity to chemotherapy in oncological patients. A better understanding of molecular network of AP-2 factors and other molecules may clarify the atypical molecular mechanisms occurring during carcinogenesis, and may assist in the recognition of new diagnostic biomarkers.

This work tests bioenergetic and cell-biological implications of the synthetic fatty acid Minerval (2-hydroxyoleic acid), previously demonstrated to act by activation of sphingomyelin synthase in the plasma membrane (PM) and lowering of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) and their carcinogenic signaling. We show here that Minerval also acts, selectively in cancer cell lines, as an ATP depleting uncoupler of mitochondrial oxidative phosphorylation (OxPhos). As a function of its exposure time, Minerval compromised the capacity of glioblastoma U87-MG cells to compensate for aberrant respiration by up-modulation of glycolysis. This effect was not exposure time-dependent in the lung carcinoma A549 cell line, which was more sensitive to Minerval. Compared with OxPhos inhibitors FCCP (uncoupler), rotenone (electron transfer inhibitor), and oligomycin (F1F0-ATPase inhibitor), Minerval action was similar only to that of FCCP. This similarity was manifested by mitochondrial membrane potential (MMP) depolarization, facilitation of oxygen consumption rate (OCR), restriction of mitochondrial and cellular reactive oxygen species (ROS) generation and mitochondrial fragmentation. Additionally, compared with other OxPhos inhibitors, Minerval uniquely induced ER stress in cancer cell lines. These new modes of action for Minerval, capitalizing on the high fatty acid requirements of cancer cells, can potentially enhance its cancer-selective toxicity and improve its therapeutic capacity.

We conducted comprehensive analyses to assess the diagnostic ability of miRNA-451 in cancers. A systematic online search was conducted in PubMed, Web of Science, China’s national knowledge infrastructure, and VIP databases from inception to July 31, 2017. The bivariate random effect model was used for calculating sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under cure (AUC). The whole pooled sensitivity and specificity were 0.85 (0.77–0.90) and 0.85 (0.78–0.90) with their 95% confidence interval (95%CI), respectively. The pooled AUC was 0.91 (95%CI: 0.89–0.94). Positive likelihood ratio was 5.57 (95%CI: 3.74–8.31), negative likelihood ratio was 0.18 (95%CI: 0.11–0.28), and diagnostic odds ratio was 31.33 (95%CI: 15.19–64.61). Among Asian population, the sensitivity and specificity were 0.85 (95%CI: 0.77–0.91) and 0.86 (95%CI: 0.78–0.91), respectively. The positive likelihood ratio and negative likelihood ratio were 5.87 (95%CI: 3.78–9.12) and 0.17 (95%CI: 0.11–0.28). The diagnostic odds ratio and AUC were 34.31 (15.51–75.91) and 0.92 (0.89–0.94). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and AUC for digestive system cancer were 0.83, 0.88, 6.87, 0.20, 35.13, and 0.92, respectively. The other cancers were 0.87, 0.81, 4.55, 0.16, 28.51, and 0.90, respectively. For sample source, the results still remain consistent. Our results indicated miRNA-451 has a moderate diagnostic ability for cancers, and could be a potential early screening biomarker, and considered as an adjuvant diagnostic index when being combined with other clinical examinations.

G4C14-A4T14 polymorphism of TP73 gene has been reported with a potential association in cancer risks through affected cell homeostasis; however the results were not consistent. We performed a comprehensive meta-analysis to explore the associations between G4C14-A4T14 polymorphism and cancer susceptibility. Extensive retrieve was performed in PubMed, EMBASE, Google Scholar, Web of Science, Wanfang database and CNKI database up to May 20, 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were conducted to evaluate the overall strength of the associations in five genetic models, as well as in subgroup analyses. Q -test, false-positive report probability analysis and trial sequential analysis, Egger’s test and Begg’s funnel plot were applied to evaluate the robustness of the results. In silico analysis was managed to demonstrate the relationship of TP73 expression correlated with cancer tissues. Finally, 36 case–control studies with a total of 9493 cancer cases and 13,157 healthy controls were enrolled into the meta-analysis. The pooled results present a significantly higher risk of G4C14-A4T14 polymorphism in all the five genetic models, as well as in the subgroups of Caucasian, cervical cancer, colorectal cancer, H-B subgroup and comfort to Hardy–Weinberg equilibrium subgroup. In silico analysis revealed that the expression of TP73 in cervical cancer tissue is higher than it in corresponding normal tissue, as well as in cervical cancer. All in all, TP73 G4C14-A4T14 polymorphism causes an upgrade cancer risk, especially in Caucasian population. G4C14-A4T14 polymorphism might be a potential biomarker for judging the tumorigenesis of cervical cancer and colorectal cancer.

Epidemiological studies have demonstrated close associations between SET8 rs16917496 T/C polymorphism and cancer risk, but the results of published studies were not consistent. We therefore performed this meta-analysis to explore the associations between rs16917496 T/C polymorphism and cancer risk. Five online databases were searched. Odds ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between rs16917496 T/C polymorphism and cancer risk. In addition, heterogeneity, accumulative, sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 13 publications involving 5878 subjects were identified according to included criteria. No significant cancer risk was observed in genetic model of SET8 rs16917496 T/C polymorphism in Asian populations (C vs. T: OR = 1.04, 95%CI = 0.88–1.23, P = 0.63%; TC vs. TT: OR = 1.17, 95%CI = 0.96–1.24, P = 0.11%; CC vs. TT: OR = 0.90, 95%CI = 0.60–1.37, P = 0.63; TC+CC vs. TT: OR = 1.11, 95%CI = 0.90–1.38, P = 0.33; CC vs. TT+TC: OR = 0.92, 95%CI = 0.65–1.30, P = 0.63). Furthermore, similar associations were found in the subgroup analysis of race diversity, control design, genotyping methods, and different cancer types. In summary, our meta-analysis indicated that the SET8 rs16917496 T/C polymorphism may not play a critical role in cancer development in Asian populations.

In the present study, we aimed at determining the potential role of rs12917 polymorphism of the O -6-methylguanine-DNA methyltransferase ( MGMT ) gene in the occurrence of cancer. Based on the available data from the online database, we performed an updated meta-analysis. We retrieved 537 articles from our database research and finally selected a total of 54 case–control studies (21010 cases and 34018 controls) for a series of pooling analyses. We observed an enhanced risk in cancer cases compared with controls, using the genetic models T/T compared with C/C ( P -value of association test <0.001; odds ratio (OR) = 1.29) and T/T compared with C/C+C/T ( P <0.001; OR = 1.32). We detected similar positive results in the subgroups ‘Caucasian’, and ‘glioma’ (all P <0.05; OR > 1). However, we detected negative results in our analyses of most of the other subgroups ( P >0.05). Begg’s and Egger’s tests indicated that the results were free of potential publication bias, and sensitivity analysis suggested the stability of the pooling results. In summary, the T/T genotype of MGMT rs12917 is likely to be linked to an enhanced susceptibility to cancer overall, especially glioma, in the Caucasian population.

Background: There is a dispute on the prognostic value of long non-coding RNA regulator of reprogramming (lncRNA ROR) in cancers. The purpose of the present study was to evaluate the prognostic significance of lncRNA ROR expression in human cancers. Methods: PubMed, Embase, and Cochrane Library were searched to look for relevant studies. The meta-analyses of prognostic and clinicopathological parameters (CPs) were conducted. Results: A total of ten studies were finally included into the meta-analysis. High lncRNA ROR expression was significantly associated with shorter overall survival (hazard ratio [HR] = 2.88, 95% confidence interval [CI] = 2.16–3.84, P <0.01) and disease-free survival (HR = 3.25, 95% CI = 2.30–4.60, P <0.01) compared with low lncRNA ROR expression. Besides, high lncRNA ROR expression was obviously related to more advanced clinical stage ( P <0.01), earlier tumor metastasis ( P =0.02), lymph node metastasis ( P <0.01), and vascular invasion ( P <0.01) compared with low lncRNA ROR expression. However, there was no significant correlation between lncRNA ROR expression and other CPs, including age ( P =0.18), gender ( P =0.33), tumor size ( P =0.25), or tumor differentiation ( P =0.13). Conclusion: High lncRNA ROR expression was associated with worse prognosis in cancers. LncRNA ROR expression could serve as an unfavorable prognostic factor in various cancers.

LINC00675 has been suggested to be dysregulated in gastric cancer, colorectal cancer and pancreatic cancer. However, the expression status and biological function of LINC00675 in glioma were still unknown. Thus, we reported LINC00675 was overexpressed in glioma tissues and cell lines, and positively associated with advanced WHO grade, large tumor size and poor prognosis. Moreover, univariate and multivariate analyses suggested that high-expression of LINC00675 was an independent unfavorable prognostic predictor for glioma. In addition, levels of LINC00675 expression were positively correlated with TRIP6 mRNA and protein expressions. The in vitro experiment showed that silencing of LINC00675 inhibits glioma cell proliferation, migration and invasion through regulating TRIP6. In conclusion, LINC00675 acts as a tumor promoter in glioma progression.

The aim of the present study was to determine whether High mobility group box 1 (HMGB1) polymorphism was associated with cancer susceptibility. PubMed, Embase, and ISI Web of Science were extensively searched without language restriction. Data were extracted using a standardized data collection sheet after two reviewers scanned studies independently. The association between HMGB1 polymorphism and cancer risks was indicated as odds ratio (OR) along with its related 95% confidence interval (95%CI). Meta-analysis was conducted via RevMan 5.3 software. A total of ten studies comprising 4530 cases and 5167 controls were included in our study. Meta-analysis revealed no statistical association between rs1045411, rs1360485, rs1412125 , or rs2249825 polymorphisms in HMGB1 gene and risk of cancer, either did subgroup analysis of rs1045411 stratified by cancer types and ethnic groups. Our results revealed no statistical association between current four polymorphism loci and cancer risks, suggesting that the attempt of applying HMGB1 variants as a therapeutic target or a prognosis predictor might still require a second thought. However, HMGB1 is deemed to play pleiotropic roles in cancers, we strongly call for large-scale studies with high evidence level to uncover the exact relationship between HMGB1 gene variants and cancer progression.

Several studies have suggested that long non-coding RNA (lncRNA) gene polymorphisms are associated with cancer risk. In the present study, we conducted a meta-analysis related to studies on the association between lncRNA single-nucleotide polymorphisms (SNPs) and the overall risk of cancer. A total of 12 SNPs in five common lncRNA genes were finally included in the meta-analysis. In the lncRNA antisense non-coding RNA (ncRNA) in the INK4 locus (ANRIL), the rs1333048 A/C, rs4977574 A/G, and rs10757278 A/G polymorphisms, but not rs1333045 C/T, were correlated with overall cancer risk. Our study also demonstrated that other SNPs were correlated with overall cancer risk, namely, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1, rs619586 A/G), HOXA distal transcript antisense RNA (HOTTIP, rs1859168 A/C), and highly up-regulated in liver cancer (HULC, rs7763881 A/C). Moreover, four prostate cancer-associated ncRNA 1 (PRNCR1, rs16901946 G/A, rs13252298 G/A, rs1016343 T/C, and rs1456315 G/A) SNPs were in association with cancer risk. No association was found between the PRNCR1 (rs7007694 C/T) SNP and the risk of cancer. In conclusion, our results suggest that several studied lncRNA SNPs are associated with overall cancer risk. Therefore, they might be potential predictive biomarkers for the risk of cancer. More studies based on larger sample sizes and more lncRNA SNPs are warranted to confirm these findings.

miRNA polymorphisms had potential to be biomarkers for cancer susceptibility and prognosis. The mature miRNA-let-7 family was considered as the most important miRNA for the cancer incidence and progression. Recently, the promising let-7 miRNAs were reported to be associated with various cancers, but the results were inconsistent. We performed a first-reported systematic review with a meta-analysis for the association of let-7 family single nucleotide polymorphisms (SNPs) with cancer risk/prognosis. Ten studies were included with a total of 3878 cancer cases and 4725 controls for the risk study and 1665 cancer patients for the prognosis study in this meta-analysis. In the risk study, the let-7i rs10877887 and let-7a-1/let-7f-1/let-7d rs13293512 were shown no significant association for the overall cancer risk. In the stratified analysis, the rs10877887 variant genotype was significantly associated with a decreased cancer risk in head and neck cancer (TC compared with TT: P =0.017; odds ratio (OR) = 0.81; TC + CC compared with TT: P =0.020; OR = 0.82). In the prognosis study, the let-7i rs10877887 SNP was shown to be associated with a higher risk for cancer prognosis in the dominate model ( P =0.004; hazard ratio (HR) = 1.32). The other two SNPs ( let-7a-1 rs10739971 and let-7a-2 rs629367) were not found to be associated with cancer survival. None of the let-7 family polymorphisms had potential to be biomarkers for cancer susceptibility but let-7i rs10877887 SNP had potential to be predicting markers for cancer prognosis. In the future, large-sample studies are still needed to verify our findings.

Evolving strategies to counter cancer initiation and progression rely on the identification of novel therapeutic targets that exploit the aberrant genetic changes driving oncogenesis. Several chromatin associated enzymes have been shown to influence post-translational modification (PTM) in DNA, histones, and non-histone proteins. Any deregulation of this core group of enzymes often leads to cancer development. Ubiquitylation of histone H2B in mammalian cells was identified over three decades ago. An exciting really interesting new gene (RING) family of E3 ubiquitin ligases, known as RNF20 and RNF40, monoubiquitinates histone H2A at K119 or H2B at K120, is known to function in transcriptional elongation, DNA double-strand break (DSB) repair processes, maintenance of chromatin differentiation, and exerting tumor suppressor activity. RNF20 is somatically altered in breast, lung, prostate cancer, clear cell renal cell carcinoma (ccRCC), and mixed lineage leukemia, and its reduced expression is a key factor in initiating genome instability; and it also functions as one of the significant driving factors of oncogenesis. Loss of RNF20/40 and H2B monoubiquitination (H2Bub1) is found in several cancers and is linked to an aggressive phenotype, and is also an indicator of poor prognosis. In this review, we summarized the current knowledge of RNF20 in chronic inflammation-driven cancers, DNA DSBs, and apoptosis, and its impact on chromatin structure beyond the single nucleosome level.

The long noncoding RNA myocardial infarction associated transcript (MIAT) is involved in a number of diseases, including myocardial infarction and diabetic retinopathy. Emerging evidence suggests that MIAT expression levels are increased in different type of cancers, including breast cancer. In the present study, we further evaluated the role of MIAT in breast cancer and investigated the consequences of its silencing on breast cancer response to chemotherapeutic agents. Expression levels of MIAT mRNA in breast cancer were determined using TissueScan™ Breast Cancer cDNA Arrays. Breast cancer cell lines were transfected with MIAT specific siRNAs, with silencing confirmed using RT-qPCR and the effects on breast cancer cell survival and response to different apoptotic stimuli determined. MIAT transcript levels were significantly elevated in breast cancer samples. Such increase was specific to the early stages of the disease, ER, PR +ve, HER –ve, and triple negative breast cancer samples. Silencing of MIAT induced growth arrest and increased basal apoptosis. Reduced levels of MIAT augmented the apoptotic response of breast cancer cells to a wide range of apoptotic stimuli. Our results also showed that MIAT down-regulation was associated with a decrease in OCT4 mRNA, suggesting the existence of a MIAT/OCT4 regulatory loop, similar to that observed in malignant mature B cells. Taken together with the recent demonstration of oncogene characteristics, our observations suggest that MIAT plays an important role in breast tumorigenesis. Strategies to decrease MIAT expression levels may improve sensitivity to therapy in breast cancer by enhancing the apoptotic responses to conventional chemotherapies.

Single nucleotide polymorphisms (SNPs) in miRNA biosynthesis genes DROSHA and DGCR8 were indicated to be correlated with cancer risk. We comprehensively reviewed and analyzed the effect of DROSHA and DGCR8 polymorphisms on cancer risk. Eligible articles were selected according to a series of inclusion and exclusion criteria. Consequently, ten case–control studies (from nine citations) with 4265 cancer cases and 4349 controls were involved in a meta-analysis of seven most prevalent SNPs (rs10719 T/C, rs6877842 G/C, rs2291109 A/T, rs642321 C/T, rs3757 G/A, rs417309 G/A, rs1640299 T/G). Our findings demonstrated that the rs417309 SNP in DGCR8 was significantly associated with an elevated risk of overall cancer in every genetic model. In stratified analysis, correlations of DROSHA rs10719 and rs6877842 SNPs were observed in Asian and laryngeal cancer subgroups, respectively. Moreover, associations of the rs417309 SNP could also be found in numerous subgroups including: Asian and Caucasian population subgroups; laryngeal and breast cancer subgroups; population-based (PB) and hospital-based (HB) subgroups. In conclusion, the DROSHA rs10719, rs6877842 SNPs, and DGCR8 rs417309 SNP play pivotal roles in cancerogenesis and may be potential biomarkers for cancer-forewarning.