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.     

结直肠癌肝转移相关microRNA的研究现状

肿瘤的转移是一个多步骤复杂的过程,肝转移是结直肠癌最常见的转移方式之一,对转移机制的理解和深入研究有助于寻求解决结直肠癌肝转移的方法,当前研究认为microRNA参与了肿瘤的转移与复发,通过对结直肠癌肝转移相关microRNA的研究,为疾病的发生发展、诊断治疗及预后等方面的研究提供了新的思路。归纳了结直肠癌肝转移相关microRNA的研究进展,回顾了microRNA的生物学功能以及分子机制,表明microRNA在肿瘤转移领域具有重要的意义,尤其在结直肠癌肝转移方面发挥着重要的作用。     

The oncogenic impact of RNF2 on cell proliferation,invasion and migration through EMT on mammary carcinoma

Mammary carcinoma (MC) is one of most common malignancy in women, and ring finger protein 2 (RNF2) possesses various roles in vast human tumors. In MC tissues as well as in cell lines RNF2 exhibited high expression, had significant association with tumor size, lymph node status, TNM stage, patients’ poor survival, and promoted cell proliferation, colony formation, cell migration and invasion of MC cell lines which was mediated by downregulation of E-cadherin protein. These data reveal that RNF2 protein plays a vital role in the development of MC and may be a potential therapy target of MC.     

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.     

The effects of miR-429 on cell migration and invasion by targeting Slug in esophageal squamous cell carcinoma

Increasing evidence indicates that microRNAs may play important roles in tumor development and may take part in different processes in different cancers. miR-429 is known as a cancer suppressor or oncogene that is dysregulated in different malignancies, including esophageal squamous cell carcinoma (ESCC). However, the effect of miR-429 in ESCC has not been fully explored. The purpose of this study was to investigate the functions of miR-429 in ESCC. qRT-PCR assays were performed to detect miR-429 expression in ESCC tissues and cell lines. To assess the effects of miR-429 on ESCC cells, wound healing and transwell assays were used. Luciferase reporter and western blot assays were employed to determine whether Slug is a major target of miR-429.Our results showed that the expression levels of miR-429 in ESCC tissues and cells were lower than in normal esophageal epithelial tissues and cells. Furthermore, overexpression of endogenous miR-429 inhibited the migration and invasion of ESCC cell lines. In addition, Luciferase reporter and western blot assays provided evidence that miR-429 can bind to the 3′ untranslated regions of Slug to regulate its expression and that of downstream epithelial-to-mesenchymal transition (EMT) markers. We found that Slug serves as a major target of miR-429. miR-429 plays a vital role in ESCC progression and represents a new therapeutic target for ESCC.     

Inhibition of miR-93 promotes interferon effector signaling to suppress influenza A infection by upregulating JAK1

Type I interferons play a critical role in host defense against influenza virus infection. Interferon cascade induces the expression of interferon-stimulated genes then subsequently promotes antiviral immune responses. The microRNAs are important regulators of innate immunity, but microRNAs-mediated regulation of interferon cascade during influenza infection remains to be fully identified. Here we found influenza A virus (IAV) infection significantly inhibited miR-93 expression in alveolar epithelial type II cells through RIG-I/JNK pathway. IAV-induced downregulation of miR-93 was found to upregulate JAK1, the target of miR-93, and then feedback promote antiviral innate response by facilitating IFN effector signaling. Importantly, in vivo administration of miR-93 antagomiR markedly suppressed IAV infection, protecting mice form IAVs -associated death. Hence, the inducible downregulation of miR-93 feedback suppress IAV infection by strengthening IFN-JAK-STAT pathway via JAK1 upregulation, and in vivo inhibition of miR-93 bears considerable therapeutic potential for suppressing IAV infection.     

miR-301b在调节脂肪细胞分化中的作用

摘要： 目的 研究 miR-301b 在调节间充质干细胞向脂肪细胞分化过程中的作用。方法 对小鼠骨髓基质细胞 ST2 进行脂肪细胞诱导分化, 并利用 qRT-PCR 检测细胞分化过程中成脂分化诱导组相对于阴性对照组的 miR-301b 表达变化。对 ST2 细胞转染 miR-301b mimics 并进行成脂诱导分化, 利用 qRT-PCR 和 Western blot 技术检测 miR- 301b mimics 转染组和阴性对照片段 （NC） 转染组细胞的脂肪特异性基因和蛋白表达水平的变化。结果 成脂分化诱导组 miR-301b 相对表达水平 （0.219±0.021） 较对照组 （1.000±0.425） 减少 （P＜0.05）。miR-301b mimics 转染组的脂肪细胞特异性转录因子过氧化物酶体增殖物激活受体 （PPARγ）、 CCAAT 增强子结合蛋白 （C/EBPα） 和脂肪型脂肪酸结合蛋白 （aP2） 的相对表达量均较 NC 转染组降低 （P＜0.05）。miR-310b mimics 转染组与 NC 转染组相比, 标志基因aP2、 转录因子PPARγ 和C/EBPα 蛋白的表达量均减少 （P＜0.05）。结论 miR-301b可抑制脂肪细胞分化。     

Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury

Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.

Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.

Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.