Circulating miR-20a and miR-26a as Biomarkers in Prostate Cancer

Objective: Circulating microRNAs (miRNAs), present in body fluids, have been considering importance as cancerbiomarkers. The primary aim of this study was to assess whether circulatory miR-20a and miR-26a can be used asdiagnostic biomarkers in prostate cancer (PCa). Methods: Relative expression miR-20a and miR-26a has been assessedin 40 patients with PCa and 40 non-cancerous volunteer. Sample Collection of patients was performed before and oneweek after prostatectomy. Total RNA was extracted from serum and miR-20a and miR-26a expressions were quantifiedby using Real-Time PCR method. Results: miR-20a was significantly up-regulated in pre-operation serum samples ofPCa patients compared to the serum samples of non-cancerous controls, however, in post-operation samples no significantdifferences was showed. miR-26a level was not significantly decreased in pre and post-operation serum samplescompared to the serum samples of controls. However, the expression level ratios of both miR-20a and miR-26a wereinsignificantly decreased when post-operation serum samples compared to pre-operation ones. Conclusion: Decrementof circulating miR-20a and miR-26a in patients after surgery may reflect the tumoral origin of those microRNAs andthe results may use for tumor remnant monitoring after prostatectomy.     

Bioinformatics Analyses of Potential miRNA-mRNA Regulatory Axis in HBV-related Hepatocellular Carcinoma

Aims: We aimed to explore the crucial miRNA-mRNA axis through bioinformatics analysis and provide evidences for the development of pathophysiological mechanisms and new therapies for HBV-related HCC.Methods: MiRNA ({"type":"entrez-geo","attrs":{"text":"GSE76903","term_id":"76903"}}GSE76903) and mRNA ({"type":"entrez-geo","attrs":{"text":"GSE77509","term_id":"77509"}}GSE77509) dataset were used to screen differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs) using R software. Overlapping genes between DE-mRNAs and target genes of DE-miRNAs were identified as candidate genes. Hub genes were obtained via cytohubba analysis. The expression at protein and mRNA levels and prognostic value of hub genes were evaluated based on The Cancer Genome Atlas (TCGA) data. Key miRNA-mRNA axes were constructed according to predicted miRNA-mRNA pairs. MiRNA expression and prognostic role were respectively identified using starBase v3.0 and Kaplan-Meier plotter database. Real-time PCR was performed to verify the expression of crucial miRNAs and mRNAs. Coexpression of crucial miRNA and mRNA were analyzed using starBase v3.0.Results: CDK1, CCNB1, CKS2 and CCNE1 were screened as hub genes, which were significantly upregulated at protein and mRNA levels. These up-regulated hub genes were also significantly associated with poor prognosis. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 were screened as critical miRNA-mRNA axes. Critical miRNAs were decreased in HCC, which indicates unfavourable prognosis. QPCR results showed that crucial miRNAs were decreased, whereas critical mRNAs were increased in HBV-related HCC. A reverse relationship between miRNA and mRNA in crucial axis was further verified.Conclusion: This study identified several miRNA-mRNA axes in HBV-related HCC. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 might serve as potential prognostic biomarkers and therapeutic targets for HBV-related HCC.     

MicroRNA profiling in serous cavity specimens: Diagnostic challenges and new opportunities

The cytomorphologic evaluation of serous cavity specimens can quickly determine the cause of an effusion as well as the presence or absence of a neoplastic process. Ancillary tests such as immunohistochemistry and fluorescence in situ hybridization are frequently used to help to definitively identify malignant cells, determine a site of origin, and distinguish between malignant and reactive mesothelial proliferations. In recent years, microRNAs (miRNAs) have been increasingly evaluated in cytologic specimens, including those from serous cavities. The examination of miRNA is attractive because of the stability of miRNA in such specimens and data suggesting that miRNA can provide prognostic and therapeutic information in addition to its role in diagnosis. Furthermore, miRNAs exist within extracellular exosomes, and this allows for their analysis in specimens that contain only rare malignant cells, degenerated cells, or obscuring components. This review discusses the technical aspects of specimen processing for miRNA analysis, recent studies of miRNA expression in malignant serous cavity specimens, and the potential importance of miRNA expression analysis for serous cavity specimens in the near future.     

肝细胞内源性microRNA与HBV交互作用影响HBV转录的机制

microRNA(miRNA)可参与转录后基因表达的调控,在调控HBV转录、复制中发挥着关键性作用。总结了肝细胞内具有抗HBV作用的miRNA及4种调控机制,HBV通过HBx及自身编码miRNA等影响肝细胞内源性miRNA表达,促进复制的机制。分析表明,肝细胞内源性miRNA与HBV交互作用构成一个复杂的调控网络,相互竞争调控的结果,决定了HBV转录的活性及疾病发展的趋势。深入研究肝细胞内源性miRNA与HBV交互作用影响HBV转录的机制,对探索新的抗HBV方法具有重要的意义。     

MicroRNAs as biomarkers and regulators of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a complicated disease affected by the interaction of environmental and genetic factors; however, the precise pathogenesis of the disease has not been fully determined. There is a need to better understand the pathogenesis of NAFLD and to identify non‐invasive diagnostic modalities. Recent advances in systematic biology and epigenetics have improved our understanding of the genotype–phenotype relationships in NAFLD. MicroRNAs (miRNAs) are important regulators of a wide range of biological processes. MiRNAs are extremely stable and protect from RNAase‐mediated degradation in body fluids, making them attractive candidate biomarkers for the early detection of the disease and the monitoring of disease progression. In this review, we summarized the current knowledge on miRNAs as potential biomarkers of NAFLD at different stages and for the prognosis of advanced diseases. Furthermore, we discussed the implications of miRNAs that functioning in lipid metabolism and hepatic steatosis as well as in hepatic inflammation and fibrosis with regard to the pathogenesis of NAFLD.     

Current frontiers in systemic sclerosis pathogenesis

Systemic sclerosis is an autoimmune disease characterised by vascular dysfunction, impaired angiogenesis, inflammation and fibrosis. There is no currently accepted disease‐modifying treatment with only autologous stem cell transplant showing clinically meaningful benefit. The lack of treatment options reflects our lack of understanding of the precise molecular mechanisms occurring in the disease. Recent investigations have begun to decipher the molecular pathways underpinning the different aspects of the disease and may provide a rational clinical target(s). Uncovering the molecular mechanisms of the disease is important in understanding systemic sclerosis treatment. The aim of this review was to examine the current thinking in SSc pathogenesis and will offer novel areas for research which may yield novel therapeutics.     

Novel epigenetic-based therapies useful in cardiovascular medicine

Epigenetic modifications include DNA methylation, his-tone modifications, and micro RNA. Gene alterations have been found to be associated with cardiovascular diseases, and epigenetic mechanisms are continuously being studied to find new useful strategies for the clinical management of afflicted patients. Numerous cardiovascular disorders are characterized by the abnormal methylation of Cp G islands and so specific drugs that could inhibit DNA methyltransferase directly or by reducing its gene expression(e.g., hydralazine and procainamide) are currently under investigation. The anti-proliferative and anti-inflammatory properties of histone deacetylase inhibitors and their cardio-protective effects have been confirmed in preclinical studies. Furthermore, the regulation of the expression of micro RNA targets through pharmacological tools is still under development. Indeed, large controlled trials are required to establish whether current possible candidate antisense micro RNAs could offer better therapeutic benefits in clinical practice. Here, we updated therapeutic properties, side effects, and feasibility of eme-rging epigenetic-based strategies in cardiovascular diseases by highlighting specific problematic issues that still affect the development of large scale novel therapeutic protocols.     

miRNA-146a rs2910164位点的单核苷酸多态性与原发性肝癌术后复发的相关性

目的探讨miRNA-146a rs2910164位点的单核苷酸多态性与肝癌术后复发的相关性。方法选取于东风医疗集团茅箭医院行肝癌根治性切除术的89例原发性肝癌患者,按照术后是否复发分为复发组和非复发组。应用Taq Man探针法对miRNA-146a rs2910164 G/C位点的基因分型,比较两组各基因型的频率及miRNA-146a的单核苷酸多态性与肝癌术后复发风险的关系。计量资料组间比较采用成组t检验,计数资料采用χ2检验,并采用多因素Logistic回归分析可能影响肝癌复发的因素。结果非复发组miRNA-146a G/C三种基因型符合Hardy-Weinberg平衡定律(P0.05)。肝癌术后复发组和非复发组miRNA-146a G/C基因型频率差异有统计学意义(χ2=9.115,P=0.010),其中复发组miRNA146a(rs2910164)CG基因型频率明显高于非复发组(χ2=4.013,P=0.039),GG基因型频率明显低于非复发组(χ2=9.046,P=0.003)。多因素Logistic分析显示肿瘤直径、miRNA146a(rs2910164)CG基因型是肝癌术后复发的危险因素(OR=1.075,P=0.003 9;OR=6.215,P=0.001 4),miRNA146a(rs2910164)GG基因型是肝癌术后复发的保护因素(OR=0.382,P=0.002 5)。结论 miRNA-146a rs2910164 C/G位点的多态性与肝癌根治术后复发相关,rs2910164位点的CG基因型可能是引起肝癌患者术后复发的危险因素。