It is suggested that miR-23a, acting as an oncogenic regulator by directly targeting APAF 1 in pancreatic cancer, is a useful potential biomarker in diagnosis and treatment of pancreatic cancer.

Results: rs920778, rs7958904 and rs874945 but not rs4759314 and rs1899663 loci were significantly related to cancer risk, among of which rs920778 and rs874945 increased and rs7958904 decreased cancer risk, respectively. Moreover, rs920778 is significantly susceptible in both Asian population and digestive cancer risks. Materials and Methods: Data were collected from PubMed, Embase and Webof Science. A total of 11 case-control studies were selected for the quantitative analysis. Software Stata (Version 12) was used to calculate Odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the strength of the associations. Subgroup analysis, sensitivity analysis, and publication bias were also performed. Five HOTAIR SNPs were finally enrolled in the study.Conclusions: HOTAIR SNP rs920778, rs7958904 and rs874945 are susceptible to cancer risk. SNP rs920778 is also a useful risk factor in evaluation of Asian population and digestive cancer. In addition, the cancer risk SNP rs874945 is first reported in the meta-analysis.

miR-27a regulates cell differentiation in a variety of diseases. However, whether and how miR-27a participates in laryngeal cancer cell differentiation remains unknown. Therefore, we explored role and molecular mechanism of miR-27a in laryngeal cancer differentiation in the study. We found that miR-27a expression was inversely correlated with laryngeal cancer differentiation degree based on the clinical pathological diagnosis of each patient. miR-27 asignificantly rescued differentiation and inhibited β-catenin, LEF1, OCT4 and SOX2 in Wnt/β-catenin pathway in all-trans-retinoic acid (ATRA)-induced laryngeal cancer cells. Bindings of RARα to miR-27a and miR-27a to GSK-3β were confirmed by ChIP and Luciferase reporter assays, respectively. In conclusion, miR-27a is a negative regulator in laryngeal cancer differentiation. RARα-mediated miR-27a transcriptional inactivation releases the inhibition of miR-27a on GSK-3β leading to laryngeal cancer differentiation through GSK-3β-involved Wnt/β-catenin pathway, suggesting that miR-27a is a usefully therapeutic target at least in ATRA-induced laryngeal cancer differentiation.

DNA methylation plays critical roles in regulation of microRNA expression and function. miR-23a-27a-24-2 cluster has various functions and aberrant expression of the cluster is a common event in many cancers. However, whether DNA methylation influences the cluster expression and function is not reported. Here we found a CG-rich region spanning two SP1 sites in the cluster promoter region. The SP1 sites in the cluster were demethylated and methylated in Hep2 cells and HEK293 cells, respectively. Meanwhile, the cluster was significantly upregulated and downregulated in Hep2 cells and HEK293 cells, respectively. The SP1 sites were remethylated and the cluster was significantly downregulated in Hep2 cells into which methyl donor, S-adenosyl-L-methionine, was introduced. Moreover, S-adenosyl-L-methionine significantly increased Hep2 cell viability and repressed Hep2 cell early apoptosis. We also found that construct with two SP1 sites had highest luciferase activity and SP1 specifically bound the gene cluster promoter in vitro. We conclude that demethylated SP1 sites in miR-23a-27a-24-2 cluster upregulate the cluster expression, leading to proliferation promotion and early apoptosis inhibition in laryngeal cancer cells.

BackgroundMicroRNA-23a (miR-23a) has been demonstrated to play an important role in the development of several types of cancer, but its role in tumorigenesis of laryngeal carcinoma is still unclear. The aim of this study was to investigate the expression patterns and clinical implications of miR-23a in laryngeal cancer.MethodsQuantitative RT-PCR was performed to evaluate the expression level of miR-23a in 52 pairs of laryngeal cancer. Analysis between miR-23a expression and clinical features of laryngeal carcinomas was performed by appropriate statistical methods. Role of miR-23a in laryngeal cancer cell migration and invasion was detected via transwell and matrigel assays, respectively.ResultsmiR-23a was significantly up-regulated in laryngeal cancer tissues compared to normal adjacent laryngeal tissues (P < 0.01). Tumors with high miR-23a expression had significantly greater extent of lymph node metastasis (P < 0.01), worse clinical stage (P < 0.05) and shorter overall five-year survival (P < 0.01) than those with low miR-23a expression. Both univariate and multivariate Cox hazard regression analysis results showed that clinical stage and miR-23a expression were significantly correlated with patient five-year survival (P < 0.01). miR-23a overexpression also significantly promoted laryngeal cancer cell migration and invasion in vitro.ConclusionsmiR-23a, an independent prognostic factor for laryngeal cancer, participates in the onset and progression of laryngeal cancer.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2021488014982305