The expression of Mirc1/Mir17–92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients

Introduction

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17–92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17–92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment.

A urinary microRNA (miR) signature for diagnosis of bladder cancer

Introduction

Bladder cancer (BC) is diagnosed by cystoscopy, which is invasive, costly and causes considerable patient discomfort. MicroRNAs (miR) are dysregulated in BC and may serve as non-invasive urine markers for primary diagnostics and monitoring. The purpose of this study was to identify a urinary miR signature that predicts the presence of BC.

β－分泌酶与阿尔茨海默病

阿尔茨海默病（A D ）是最常见的一种痴呆症,主要临床特点为进行性认知功能下降,最终导致身体机能的下降甚至死亡,65岁以上的老年人群多发［1］。对于年轻家族性AD患者而言,AD的发生与多基因因素相关,而对于年老的散发性AD患者,其原因是多重性的,包括基因、环境和后天造成的基因改变等因素。尽管AD的病因不明,但患者脑内β－淀粉样蛋白（Aβ）的增多可能是导致此病的首要原因。Aβ主要是由β－淀粉样前体（APP ）在β－分泌酶（BACE1）的作用下使其在β位点发生裂解而产生,这一过程在AD的病理性神经纤维缠结和淀粉样斑块形成中发挥着重要作用［2］。AD患者中BACE1的表达和活性均有显著升高［3］,已成为诊断AD的一个重要生物指标［4］。而关于BACE1的了解目前还存在很多局限,现通过以下几个方面来讨论近年BACE1在AD中的有关研究进展。     

Predisposition to treatment response in major depressive episode: A peripheral blood gene coexpression network analysis

Antidepressant efficacy is insufficient, unpredictable and poorly understood in major depressive episode (MDE). Gene expression studies allow for the identification of significantly dysregulated genes but can limit the exploration of biological pathways. In the present study, we proposed a gene coexpression analysis to investigate biological pathways associated with treatment response predisposition and their regulation by microRNAs (miRNAs) in peripheral blood samples of MDE and healthy control subjects. We used a discovery cohort that included 34 MDE patients that were given 12-week treatment with citalopram and 33 healthy controls. Two replication cohorts with similar design were also analyzed. Expression-based gene network was built to define clusters of highly correlated sets of genes, called modules. Association between each module’s first principal component of the expression data and clinical improvement was tested in the three cohorts. We conducted gene ontology analysis and miRNA prediction based on the module gene list. Nine of the 59 modules from the gene coexpression network were associated with clinical improvement. The association was partially replicated in other cohorts. Gene ontology analysis demonstrated that 4 modules were associated with cytokine production, acute inflammatory response or IL-8 functions. Finally, we found 414 miRNAs that may regulate one or several modules associated with clinical improvement. By contrast, only 12 miRNAs were predicted to specifically regulate modules unrelated to clinical improvement. Our gene coexpression analysis underlines the importance of inflammation-related pathways and the involvement of a large miRNA program as biological processes predisposing associated with antidepressant response.     

MicroRNA在人结肠癌干细胞中的表达谱

目的:探讨微小RNA(microRNA,miRNA)在人结肠癌干细胞中的表达,为进一步研究miRNA调控结肠癌干细胞向结肠癌细胞分化的分子机制奠定基础.方法:应用miRNA表达谱芯片检测人结肠癌干细胞和已分化结肠癌细胞中miRNA的表达谱.利用实时定量PCR技术检测两种细胞中差异表达的miRNA,验证miRNA芯片结果的可靠性.应用软件对筛选出的显著差异表达miRNA的靶基因进行预测.结果:与已分化结肠癌细胞相比,人结肠癌干细胞中表达上调超过1.5倍的miRNA有35个.为:hsa-miR-192,hsa-miR-29b,hsa-miR-215,hsa-miR-194,hsa-miR-33a,hsa-miR-32等:表达下调超过1.5倍的miRNA有11个,为:hsa-miR-93,hsa-miR-1231,hsa-miR-524-3p,hsa-miR-886-3p等.PCR技术验证,与miRNA芯片结果相符合.表达显著上调miRNA的共同靶mRNA有:AFF2、MTF1、RUNDC2C和ZFHX4.表达显著下调miRNA的共同靶mRNA有:ONECUT2、SH3TC2、PTPRT、RNABP10、NR3C1、RGSL1、RNASEL和TANC2.结论:筛选出的差异表达miRNA可能参与结肠癌的发病.为该病诊治提供了新的思路.其共同靶基因可能具有重要的调控结肠癌干细胞生长和分化的作用.     

微小RNA与肿瘤耐药

 【摘要】　微小RNA （miRNA）是近年来在真核生物中发现的、在转录后水平负调控基因表达的一类长约22个核苷酸的非编码小分子RNA。miRNA生物学效应广泛,与细胞生长、凋亡、新陈代谢和信号转导等密切相关。已报道miRNA在各种肿瘤中表达失常,可能发挥着癌基因和抑癌基因的双重作用,同时越来越多的研究表明miRNA在调节肿瘤细胞对抗肿瘤药物耐药方面发挥着重要作用。系统深入地研究miRNA在肿瘤耐药中的机制,将为发展基于miRNA逆转肿瘤耐药的治疗策略提供重要的依据。     

实时荧光定量PCR方法检测石蜡包埋组织microRNA表达的方法探讨

目的:探讨从石蜡包埋组织中运用实时荧光定量PCR(RQ-PCR)方法检测microRNA表达的可靠性和敏感性。方法:选取2005年至2010年从石河子大学医学院第一附属医院、新疆伊犁哈萨克族自治州友谊医院收集的97例福尔马林固定、石蜡包埋食管癌组织样本,提取组织总RNA,RT-PCR逆转录为cDNA,实时荧光定量PCR法检测microRNA表达。结果:97例食管癌组织样本中,RNA提取成功90例,7例失败,运用实时荧光定量PCR成功检测了83例microRNA表达,7例检测不准确。RNA提取成功率明显高于失败率,实时荧光定量PCR检出的定量准确例数高于定量不准确例数,P<0.05,差异具有统计学意义。结论:实时荧光定量PCR(RQ-PCR)方法是检测石蜡包埋组织中microRNA表达的一种有效方法。     

胃窦癌患者幽门螺旋杆菌感染率与MiR-21表达水平的相关性

目的探讨胃癌患者幽门螺旋杆菌(Helicobacter pylori,Hp)感染率与miR-21表达水平的相关性。方法2011-01/2012-01月求诊广州军区广州总医院消化内科的患者,经电子胃镜检查,活检其病变组织送病理检查,纳入诊断为胃窦癌的患者91例,慢性浅表性胃窦炎患者95例。两组患者均行13 C呼气试验,明确Hp感染情况。胃窦癌患者转外科行手术根治,术中留取病变组织及癌旁组织,应用实时荧光定量聚合酶链反应(real time fluorescence qua-ntitativepolymerase chain reaction,qRT-PCR)进行miR-21表达水平检测。结果①胃癌患者Hp感染率为79.12%,高于慢性浅表性胃窦炎组的66.32%,差异有统计学意义(P=0.001);②胃癌患者的胃癌组织miR-21表达水平较癌旁组织高,差异有统计学意义(P=0.000);③感染Hp的胃癌患者miR-21表达水平较Hp阴性患者高,差异具有统计学意义(P=0.009)。结论Hp感染、miR-21高表达可能共同参与胃癌的发生、发展,二者存在相关性。