MicroRNA profiling in periampullary carcinoma

BackgroundMicroRNA expression patterns in many physiological and oncogenic processes have been established. However, the role of aberrant miRNA expression in periampullary carcinoma (PAC) has not been elucidated. We hypothesize that PAC may have differential expression of miRNAs which may differentiate the tumor histological subtypes.MethodsFresh paired tumor and control samples were collected from the PAC patients undergoing Whipple's pancreaticoduodenectomy. Microarray miRNA profiling was performed utilizing tumor (n = 40) and control tissues; adjacent normal pancreas (n = 22), six each distal CBD, duodenum and ampulla. Data obtained was subjected to statistical and bioinformatic analysis. Differentially expressed miRNAs obtained were validated using qPCR in an independent set of samples.ResultsComparison of PAC tissue samples with controls revealed 29 common and differentially expressed miRNAs (20 upregulated and 9 downregulated) with a higher statistical significance (p < 0.001) and fold change (log2 FC > 1.5). A subset of 16 miRNAs (15 overexpressed and 1 underexpressed) differed in expression levels between pancreatobiliary and intestinal subtypes. Among these, miR-375, miR-31 and miR-196a expressions varied significantly between histological subtypes. Differential expression profiles of miRNAs specific to TNM staging was also observed in PAC subtypes. Target gene prediction for the differentially expressed miRNAs in PAC revealed that target genes are enriched for certain pathways. Particularly, Wnt signaling pathway genes appear to be relevant targets for most of the differentially expressed miRNAs.ConclusionDifferentially expressed common miRNA signatures identified in PAC subgroups may have a role in pathogenesis of PAC and miR-375, miR-31 and miR-196a expression patterns may differentiate PAC subtypes.     

miRNA在心血管疾病中的研究进展

MicroRNAs（miRNAs）是一类长度为21~25个核糖核苷酸的非编码内源性小单链RNAs分子,在转录后水平调控蛋白质的表达,几乎参与所有生命体的生理和病理过程。最近研究显示miRNAs在心血管系统发生及病理生理方面发挥至关重要作用。循环miRNAs概念的引入,使得对其研究变得更加方便,可能作为新的心血管疾病生物标志物。本文就miRNA在心血管方面的研究进展加以综述。     

心肌缺血预适应大鼠循环血微囊泡中miRNAs 表达谱分析

目的:分离提取心肌缺血预适应（IPC）模型大鼠循环血中的细胞微囊泡（MVs）,探究IPC处理对循环血MVs中microRNAs （miRNAs）表达的影响。方法:健康雄性Wistar 大鼠8只,随机分为IPC-MVs组和假手术对照（Sham-MVs）组,每组4 只。建立 大鼠心肌IPC 模型,提取循环血IPC-MVs,采用Microarray 分析两组循环血MVs 中的miRNAs,利用生物信息学进行靶基因预 测及功能分析。结果: 与Sham-MVs组比较,IPC-MVs组中循环血差异表达显著上调的miRNAs 共3 个（P<0.01,FER<0.05）: miR-1-3p、miR-133a-3p 和miR-133b-3p（t=3.194、3.002、3.389,均P<0.05）。基因本体研究会数据库（GO）和京都基因与基 因组百科全书（KEGG）分析显示,这些miRNAs 可能通过调节心肌细胞中丝裂原活化蛋白激酶（MAPK）信号通路和Ras信号 通路,发挥抗心肌缺血/再灌注（I/R）损伤的保护作用,可能参与调控的核心靶基因包括Ntrk2、Igf1、Gnai3 和Bcl2l1。结论:IPC 处 理可使大鼠循环血MVs中miR-1-3p、miR-133a-3p 和miR-133b-3p表达显著上调。     

Regulation of microRNAs by rape bee pollen on benign prostate hyperplasia in rats

The miRNAs are dysregulated in BPH. Rape bee pollen (RBP) is used to improve benign prostatic hyperplasia (BPH). Whether RBP treats BPH by regulating the dysregulated miRNAs remains unclear. Here, we identified miRNAs regulated along with the improvement of BPH by RBP in posterior lobes of prostate in rats. Firstly, to screened miRNAs might relate to improvement of BPH by RBP, we compared differentially expressed miRNAs between BPH model group and RBP group by high-throughput sequencing. As a result, 10 known miRNAs and 17 novel miRNA were up-regulated in RBP group, and 6 known and 13 novel miRNAs were down-regulated. Secondly, among the known miRNAs, we identified those that might relate to BPH by RT-qPCR, while only rno-miR-184 was screened, so we compared it among normal control group, BPH model group and RBP group. The results showed that rno-miR-184 was significantly lower expressed in BPH group, but up-regulated along with the improvement of BPH by RBP. Moreover, expression level of rno-miR-184 was no difference between RBP group and normal control level. Therefore, we considered that RBP might improve BPH through regulating expression of miRNAs like rno-miR-184 in prostate in rats.     

外泌体介导的细胞间通讯在炎症性肠病中作用的研究进展

炎症性肠病(IBD)是一种慢性非特异性免疫的肠道疾病,具有家族聚集性,可发生在任何年龄。外泌体(Exosomes)是细胞分泌/衍生的囊泡状纳米颗粒,其介导了一种新型的细胞间通讯方式,在IBD的发生和过程中发挥着重要作用。细胞分泌型mRNA和microRNAs(miRNAs)可随着外泌体在细胞间进行功能转移,并被送入受体细胞作为内源性miRNAs发挥作用,同时调节多个目标基因或信号。越来越多的证据表明,外泌体等外囊泡介导的细胞间通讯以及肠道微生物群—宿主细胞通讯参与了IBD发生、发展相关的病理状况。在这篇文章中,我们将回顾外泌体在细胞间通讯的方式作用,并详细讨论外泌体在IBD的发病机制、病情进展、治疗诊断中的作用以及其临床应用前景。     

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.     

Prognostic urinary miRNAs for the assessment of small renal masses

BackgroundRenal cell carcinoma (RCC) is often detected incidentally as a small renal mass (SRM; pT1a, ≤4 cm). It is clinically challenging to predict progression in patients with SRMs. This is largely due to the recent recognition of clinically progressive and non-progressive RCC-SRMs. It is critical to accurately stratify SRM patients according to risk to avoid unnecessary treatment. This is especially significant for elderly and infirm patients, where the risk of surgery outweighs mortality from SRMs.MethodsWe employed a qRT-PCR array-based approach and targeted qRT-PCR to identify and validate early, non-invasive diagnostic and prognostic biomarkers of RCC-SRMs. In total, we evaluated eighty urine samples, including 30 renal oncocytoma (≤4 cm) cases, 26 progressive and 24 non-progressive clear cell RCC-SRM (ccRCC-SRM) cases.ResultsWe identified nine urinary miRNAs which displayed significantly elevated expression in ccRCC-SRMs (pT1a; ≤4 cm) relative to renal oncocytoma (≤4 cm). Additionally, miR-328-3p displayed significantly down-regulated expression in progressive relative to non-progressive ccRCC-SRMs. Patients with elevated miR-328-3p expression had significantly longer overall survival (HR = 0.29, 95% CI = 0.08–1.03, p = 0.042) compared to patients with low miR-328-3p expression. We also found no significant association between miR-328-3p expression levels and gender, age, laterality, tumor size, or grade, suggesting that miR-328-3p is an independent prognostic biomarker.ConclusionsOur in-depth miRNA profiling approach identified novel biomarkers for early-stage ccRCC-SRMs. Pretreatment characterization of urinary miRNAs may provide insight into early RCC progression and could potentially aid clinical decision-making, improving patient management and reducing overtreatment.     

Polymorphism in miRNA-1 target site and circulating miRNA-1 phenotype are associated with the decreased risk and prognosis of coronary artery disease

MiRNA molecules have been identified to play key roles in a broad range of physiologic and pathologic processes. Polymorphisms in microRNA target sites (PolymiRTSs) can disturb or obstruct miRNA binding and consequentially influence regulation of the target genes. A two-step study design was used in this study. A case-control study was designed to assess the relationship between miRNA-1 target site rs9548934C→T polymorphism in target gene (Component of Oligomeric Golgi Complex 6, COG6) and risk of coronary artery disease (CAD) in 1013 patients and 610 normal controls. This genetic variant was also evaluated for the association with major adverse cardiovascular events (MACE) of CAD in a follow-up study, including 785 (785/1013) patients followed up for 42 months. The phenotypes of circulating miRNA-1 levels in 34 cases were slightly lower than that of 40 controls but not significantly different (P = 0.090). The CT and CT/TT genotypes were associated with a 34% and 26% decreased risk of CAD, and the TT and CT/TT genotypes were associated with a 76% and 49% decreased risk of MACE of CAD. Cox regression analysis showed that rs9548937 C/T variant was associated with a decreased risk of MACE, while age, diabetes mellitus, higher levels of CRP (≥ 3.80 mg/L) and three pathological changes in the coronary artery were associated with an increased risk of MACE. Our findings implicate miRNA-1 target site rs9548934C→T genotypes, circulating miRNA-1 phenotype and CRP levels may modulate the occurrence and MACE of CAD.