miRNA polymorphisms and risk of premature coronary artery disease

ObjectiveSeveral microRNA (miRNA) polymorphisms have been associated with susceptibility to specific health disorders, including cardiovascular diseases. The aim of the present study was to investigate whether four well-studied miRNA polymorphisms in non-Caucasian populations, namely miR146a G>C (rs2910164), miR149 C>T (rs2292832), miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), contribute to the risk for the development of premature Coronary Artery Disease (CAD) in the Greek population.MethodsWe used a case-control study to examine these associations in 400 individuals: 200 CAD patients [including a subgroup of myocardial infraction (MI) patients] and 200 healthy controls, all of Greek origin. MiRNA polymorphisms were genotyped using three different assays: Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), High resolution Melting (HRM) and Sanger sequencing.ResultsTwo of these polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444) were found to be strongly associated with increased risk for CAD (p=0.0388 and p=0.0013, respectively) and for MI (p=0.0281 and p=0.0273, respectively). Furthermore, miR146C-miR149C-miR196T-miR499G allele combination appeared to be significantly related to CAD (p=0.0185) and MI (p=0.0337) prevalence.ConclusionsOur results suggest that at least two of the studied polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), as well as the miR146C-miR149C-miR196T-miR499G allele combination could represent useful biomarkers of CAD and/or MI susceptibility in the Greek population. These special genetic characteristics, in combination with environmental factors and personal habits, might contribute to CAD and/or MI prevalence.     

肿瘤相关性microRNA研究进展

microRNA是一类长约19~25 nt, 能在转录后水平负性调节靶mRNA表达的小分子非编码单链RNA。它们广泛存在于真核生物体内，参与生物体发育过程中细胞分化、增殖、凋亡等多种生理病理途径的调控。 microRNA与肿瘤相关基因表达的调控密切相关，直接或间接影响肿瘤细胞的增殖与凋亡过程。     

MicroRNAs途径在RAW264.7细胞中作用的初步研究

目的通过检测microRNAs生成的关键酶Dicer在RAW264.7细胞不同功能状态下的表达差异研究microRNAs途径在其中产生的作用。方法采用QRT-PCR、流式细胞术等对RAW264.7细胞在不同功能分化状态下的Dicer酶进行检测。结果GMCSF与MCSF分别刺激RAW264.7细胞诱导其增殖分化后,Dicer酶的mRNA水平显著增高,但随刺激时间呈现不同趋势(P<0.01);在诱导凋亡死亡状态下,RAW264.7中Dicer酶的表达下降30%(P<0.01);LPS与IL-4分别诱导RAW264.7细胞分化为M1和M2型,Dicer的表达与M1、M2型相关炎性因子的表达有相关性。结论 MicroRNAs调控途径参与并影响RAW264.7不同功能状态。     

A five‐miRNA expression signature predicts survival in hepatocellular carcinoma

The aim of this study was to identify a microRNA (miRNA) expression signature for predicting HCC (hepatocellular carcinoma) survival. A total of 322 HCC patients in The Cancer Genome Atlas (TCGA) database were randomly divided into training and testing set. miRNAs, associated with survival time in the training set, were identified by using univariate Cox regression analysis. The risk score was formulated based on the expression levels of these miRNAs. Then the miRNA signature was validated in testing set through Kaplan–Meier analysis and log‐rank test. hsa‐miR‐301a, hsa‐miR‐132, hsa‐miR‐212, hsa‐miR‐489, and hsa‐miR‐1468 were identified to formulate risk score in training set and used to calculate the risk score of each patients in testing set. About 161 patients in testing set were segregated into high‐ and low‐risk group according to the median risk score. The survival time of high‐risk group was significantly shorter (p = 0.0248) than low‐risk group in testing test. The target genes of five miRNAs were significantly enriched in valine, leucine, and isoleucine degradation pathway and PPAR signaling pathway. hsa‐miR‐1468 had an up‐regulated tendency in HCC tissues compared to adjacent tumor tissues. The expression of hsa‐miR‐301a, hsa‐miR‐132, hsa‐miR‐212, hsa‐miR‐489, and hsa‐miR‐1468, which might be potential biomarkers to evaluate HCC patients' prognosis.     

JCL roundtable: Lipids and inflammation in atherosclerosis

Clinical effort in lipidology focuses largely on mitigating effects of atherosclerosis, a pathologic process localized to the intimal layer of larger arteries. This JCL Roundtable brings together 3 leading researchers to discuss the current understanding of pathogenesis in atherosclerosis. We begin by recognizing that low density lipoprotein concentrations in arterial intima far exceed concentrations in other connective tissues, consistent with the response-to-retention hypothesis of atherogenesis. High density lipoproteins facilitate reverse cholesterol transport and also have antioxidant and anti-inflammatory roles. New evidence points to remnants of triglyceride-rich lipoproteins as promoters of atherogenesis, highlighted by deleterious effects of apolipoprotein C-III. The multifaceted role of inflammation is becoming clearer through discoveries related to leukocyte recruitment, efferocytosis, resolution of inflammation, and crystal formation. MicroRNAs represent a new, complex mode of gene regulation bearing on lipoprotein and inflammation biology. Progress in understanding atherosclerosis portends a future in which residual risk related to obesity, diabetes, and other factors will yield to new targeted therapies.     

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.     

microRNAs在心肌肥厚中的作用

生理或病理性刺激会导致心肌肥厚性生长,表现为心肌细胞增大,蛋白合成增加及胎儿基因的再表达。在心脏中有很多信号分子影响着基因表达、细胞凋亡、细胞因子释放等病理生理过程。利用心肌细胞肥厚模型已经发现病理性心肌肥厚可以被抑制或逆转,这些发现为寻找调控心肌肥厚的因子及信号通路提供了基础。该文着重讨论近年来发现的microRNAs(miRNAs)在调节心肌肥厚中的作用。     

microRNA对周围神经再生的调控作用

microRNA(miRNA)是高度保守的内源性非编码RNA,在多种生理和病理过程中起着重要的作用。周围神经损伤后,许多miRNA的表达发生显著变化。差异表达的miRNA负向调控其靶基因的表达,从而影响受损周围神经的再生和重塑。本综述从miRNA对神经元、施万细胞、失神经支配肌肉等的影响,阐明miRNA在周围神经过程中的调控作用。对于miRNA在周围神经损伤和再生过程中作用的研究,有助于更好地理解周围神经损伤后的内在分子调控机制,为将miRNA作为临床治疗的靶点提供了坚实的基础。     

Differential expression of microRNAs in shrimp Marsupenaeus japonicus in response to Vibrio alginolyticus infection

Till date numerous microRNAs (miRNAs) have been discovered from various organisms, including mammals, plants, insects, nematodes and viruses. They are known to have antiviral functions in crustaceans such as shrimp Marsupenaeus japonicas. However, little is known about the role of miRNAs against bacterial infection in this shrimp caused by Vibrio alginolyticus. We performed small RNA sequencing to characterize the differentially expressed microRNAs in V. alginolyticus challenged shrimp, in comparison to that in control uninfected shrimp, at 24 h and 48 h. In total, 55 host miRNAs were differentially expressed in response to the infection and most of these were downregulated at both the time-points. TargetScan and miRanda algorithms showed that the target genes of these down-regulated miRNAs were related to innate immune functions such as production of phenoloxidase enzyme, apoptosis and phagocytosis. Further, gene ontology analysis revealed that many immune signaling pathways were mediated by these miRNAs. This study is one of the earliest attempts at characterizing shrimp miRNAs that respond to V. alginolyticus infection, and will help unravel the miRNA pathways involved in antibacterial action in shrimp.