microRNA-223在动脉粥样硬化发生过程中的网络调控机制

microRNA-223(miR-223)是参与动脉粥样硬化（atherosclerosis,AS）炎性调控、细胞生长等通路的微小非编码RNA。本研究系统地探究miR-223及其靶基因的网络调控机制,以便全面理解miR-223在AS中的作用。利用miRNA靶基因预测数据库miRDB、miRmap、TargetScan和miRTarBase获取miR-223的靶基因集。R语言分析基因表达综合数据库（gene expression omnibus,GEO）共享平台动脉粥样硬化斑块差异表达基因集（GSE100927）,筛选出斑块差异表达基因,并与miR-223靶基因集交叉匹配。利用基因本体（gene ontology,GO）及基因组数据库（kyoto encyclopedia of genes and genomes,KEGG）分析研究差异表达基因功能。结果显示,斑块中下调的1 584个差异表达基因与miR-223靶基因交叉匹配得到422个交集mRNA。GO及KEGG富集分析发现miR-223可能通过细胞生长、炎症反应以及血管平滑肌收缩等信号通路调节动脉粥样硬化斑块的发生发展过程。蛋白相互作...     

基于microRNA共调控网络的microRNA调控机制研究

已有研究通过计算和实验的手段,证明了不同的microRNA(miRNA)通过相互之间的合作,来共同调控它们所共有的靶基因。对miRNA之间这种合作行为的特性的研究,能够帮助我们更好的理解miRNA的调控机理。本文建立了一个网络来描述miRNA之间的合作关系,并通过对该网络的分析,得出了四点关于miRNA调控机制的性质。第一,基因靶标数目越多的miRNA倾向于与越多的miRNA伙伴进行合作。第二,进化上保守的miRNA所具有的共调控伙伴的数目显著多于非保守的miRNA。第三,以上的性质是跨物种的存在的(人与小鼠)。第四,miRNA与蛋白质在系统层面性质存在一定的相似。     

miR-155的研究进展

microRNA是广泛存在于真核生物中的非编码小RNA,长度为19～24nt,它能在转录后水平抑制靶基因的表达或翻译.近年来研究揭示,miR-155是一个典型的多功能基因,由其下游基因介导,参与多种生理病理过程,如炎症、免疫和肿瘤的发生、发展.本文就miR-155的主要特点及其功能的研究进展予以综述.     

循环内皮微粒相关microRNA在巨噬细胞炎性反应诱发动脉粥样硬化发生中的作用机制

目的研究循环内皮微粒相关microRNA在巨噬细胞炎性反应诱发动脉粥样硬化（AS）发生的作用机制。 方法选取实验组和对照组SPF级5周小鼠各50只。实验小鼠分4组：对照组、动脉粥样硬化模型组（AS模型组）、NC-miRNA组和miRNA-19b抑制剂组,采用油红染色对AS病变的组织学进行观察,计算斑块面积相对比例,并检测生化指标的表达水平,主要包括血清中高密度脂蛋白胆固醇（HDL-C）、胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和甘油三酯（TG）,ELISA检测血管炎症因子TNF-α、IL-1、IL-6和IL-10的变化,Western Blot检测凋亡相关蛋白Bcl-2、cleaved-caspase-3和Bax表达的变化,实时荧光定量PCR检测miR-19b表达,流式细胞法检测巨噬细胞的凋亡率。多组间比较采用单因素方差分析或者重复测量的方差分析,两两比较采用LSD-t检验。 结果各组胸腔动脉斑块面积百分比：对照组为（0.00±0.00）%;AS模型组为（9.59±6.53）%;NC-miRNA组为（8.96±3.47）%;miRNA-19b抑制剂组为（3.21±2.03）%,三组间比较差异有统计学意义（F = 20.572,P = 0.002）。与对照组比较,AS模型组和NC-miRNA组TC[AS模型组（3.26±0.21）mmol/L;NC-miRNA组（3.13± 0.14）mmol/ L;F = 13.994,P = 0.002]、TG[AS模型组（0.25±0.06）mmol/L;NC- miRNA（0.21±0.02）mmol/L;F = 11.230,P = 0.011）]和LDL-C [AS模型组（1.65±0.11）mmol/ L;NC-miRNA （1.59± 0.27）mmol/L;F = 10.069,P = 0.006）]水平升高,而HDL-CAS模型组[（0.08±0.09）mmol/L;NC-miRNA （0.08±0.05）mmol/L;F = 12.450,P = 0.004）]水平含量降低。与模型组比较,miRNA-19b抑制剂组TC（1.85±0.06）mmol/L、TG（0.15±0.03）mmol/ L和LDL-C（1.21±0.10）mmol/L水平降低,HDL-C （0.11±0.05）mmol/L水平则升高（P均< 0.05）。AS模型组与对照组相比,IL-1（34.06±3.58）g/L、IL-6（92.57±31.97）g/L和TNF-α（63.01±15.65）g/L水平升高,而IL-10（16.86±1.29）g/L的水平降低,NC-miRNA组各指标亦有相同的变化趋势;miRNA-19b抑制剂组IL-1（24.85±6.21）g/L、IL-6（53.29±17.15）g/ L和TNF-α（34.51±6.47 ）g/L水平低于AS模型组和NC-miRNA组（F = 13.671,P = 0.002）,IL-10（24.94±4.72）g/L的水平则高于两组（F = 13.675,P = 0.008）。和对照组相比,AS模型组和NC- miRNA组的Bax（AS模型组3.39±0.01;NC-miRNA组0.64±0.02;F = 26.910,P = 0.000）和cleaved-PARP （AS模型组2.47±0.05;NC- miRNA组3.27±0.01;F = 13.226,P = 0.000）表达量升高。但Bcl-2（AS模型组0.67±0.02;NC-miRNA组0.64±0.02;F = 12.585,P = 0.000）表达水平下调。与NC- miRNA组相比,miRNA-19b抑制剂组的促细胞凋亡的蛋白Bax（2.16±0.02）和cleaved-PARP（1.91±0.04）表达水平下调,Bcl-2（1.05±0.01）的表达水平上调。与对照组比较,AS模型组（2.71±0.02）和NC-miRNA组（2.43±0.02）的miRNA- 19b的转录水平增加,差异有统计学意义（P均< 0.05）,miRNA-19b抑制剂组（1.52±0.01）转录水平有升高,但相较于AS模型组和NC-miRNA组的变化其增加量不显著,（F = 15.353,P = 0.002）。miRNA-19b基因转录水平：对照组为1.02±0.03;AS模型组为2.71±0.02;NC- miRNA组为2.43±0.02;miRNA- 19b抑制剂组为1.52±0.01（P均 < 0.05）。细胞凋亡率：对照组为（4.41±0.18）%;AS模型组为（7.16±0.73）%;NC-miRNA组为（6.29±0.24）%;miRNA-19b抑制剂组为（5.01±0.11）%,（F = 12.889,P = 0.008）。 结论miRNA-19b抑制剂可以减少巨噬细胞的凋亡,降低促炎症因子,可减少由于AS引起的血管厚度的增加,减少AS斑块的面积比例,使血脂中的TC、TG和LDL-C水平降低,HDL-C水平则有升高,这对冠心病的临床诊疗具有重要的临床指导意义。     

microRNA-155研究进展

microRNAs(miRNAs)是一类进化上保守的非编码单链小RNA,长19～24个核苷酸,能在转录后降解靶基因mRNA或抑制基因的翻译。microRNA-155(miR-155)具有多种生物学功能,它能影响造血细胞的分化,并在炎症反应、免疫反应中发挥重要作用。大量研究表明,miR-155在多种肿瘤细胞中过表达,推测其与肿瘤的发生发展密切相关。随着研究的深入,miR-155可能成为新的肿瘤标志物及肿瘤基因治疗的新靶点。     

microRNA调控的生物网络

生物网络是生物体内各种分子通过相互作用来完成各种复杂的生物功能的一个体系。网络水平的研究,有助于我们从整体上理解生物体内各种复杂事件发生的内在机制。microRNA（miRNA）是一类在转录后水平调控基因表达的小RNA分子。研究结果表明,miRNA调控的靶基因分布范围很广,因此必然与目前所研究的生物网络有着各种各样的联系。对这种关系的揭示,将对阐明miRNA的调控规律起到重要的作用。本文重点讨论了miRNA调控的基因调控网络、蛋白质相互作用网络以及细胞信号传导网络的特征。此外,还总结了miRNA调控的网络模体（motif）和miRNA协同作用网络的特征。     

microRNA调控网络与肿瘤

microRNA(miRNA)是一类长度约为22nt的小分子非编码RNA,对基因表达进行转录后调控。基因调控网络由各种回路,如前馈和反馈回路组成。它通过将外界刺激整合成合适的输出信号,控制细胞从增殖到死亡几乎所有的生命活动。已知基因调控网络的失调与肿瘤的发生发展密切相关。新近的实验证据表明,miRNA广泛参与基因调控网络中的反馈和前馈回路。该文主要介绍miRNA在基因表达调控网络中的作用及其与肿瘤发生发展的关系。     

炎症小体在动脉粥样硬化发生发展中的研究进展

炎症小体(inflammasome)是免疫细胞内由多种蛋白质所组成的复合体,属于胞浆型模式识别受体(pattern recognition receptor,PRR)。它作为固有免疫系统的重要组分在机体免疫反应和疾病发生过程中具有重要作用。近年来的研究表明炎症小体是炎症免疫反应的核心。由于能被多种类型的病原体或危险信号所激活,NLRP3(NOD样受体蛋白-3)炎症小体在多种疾病过程中,包括动脉粥样硬化症、家族性周期性自身炎症反应、阿尔海默茨病和2型糖尿病等都发挥了关键作用。因此,NLRP3(NOD样受体蛋白-3)炎症小体可能为各种炎症性疾病,包括动脉粥样硬化的治疗提供新的靶点。本文将对炎症小体在动脉粥样硬化发生发展中发挥的作用进行综述。     

miR-155在常见病原微生物感染中的研究进展

microRNAs(miRNAs)是一类长度为17~25 nt,进化上保守的非编码单链小RNA,成熟的miRNAs通过碱基互补配对的方式识别靶mRNA,并根据互补程度介导沉默复合体降解靶mRNA或者阻遏靶mRNA的翻译。miR-155是miRNAs家族中的典型代表,其不仅参与调控肿瘤细胞的增殖、分化和凋亡,而且在微生物感染过程及免疫炎症反应中也发挥着重要作用。将对miR-155在常见的几种病原微生物感染过程中发挥的作用做系统综述。     

乳腺癌致病microRNA调控网络的识别与生物信息学分析

目的:构建并解析乳腺癌致病microRNA(miRNA)调控网络,探究其在乳腺癌发生发展中的调控机制。方法:整合TCGA、ENCODE、Fantom等公共数据库资源,得到miRNA、转录因子和基因候选调控关系数据,结合差异表达、变异系数与PCA,构建乳腺癌miRNA调控网络,解析调控网络的度中心性与聚类系数,使用DAVID进行功能富集分析,构建Cox回归模型作生存曲线。结果:共识别miRNA调控网络262个,其中包含5个显著差异表达miRNA,8个转录因子和130个基因。通过功能富集分析发现这些miRNA靶基因显著参与细胞周期、细胞分化、细胞生长、转移等转录后调控的肿瘤生物进程,并与FoxO信号通路、p53信号通路、基因监测通路等信号通路高度相关。通过分析生存曲线发现hsa-mir-144与hsa-mir-133a-2显著与乳腺癌患者生存相关。结论:识别的乳腺癌致病miRNA调控网络中miRNA之间有相互作用,且网络整体功能不仅受hub网络影响,也受元件自身特性影响,这些miRNA靶基因显著富集于肿瘤相关生物学进程与信号通路中。     

The Role of MicroRNA-155 in Chlamydia muridarum Infected lungs

Our laboratory has investigated the role of an evolutionarily conserved RNA species called microRNAs (miRs) in regulation of anti-chlamydial protective immunity. MiRs including miR-155 expressed in specific immune effector cells are critical for antigen specific protective immunity and IFN-γ production. Using miR-155 deficient mice, and a murine pulmonary model for chlamydial infection, we report here 1) the effect of host miR-155 on bacterial burden, and 2) identify probable immune genes regulated by miR-155.     

Long noncoding RNA MIR155HG facilitates pancreatic cancer progression through negative regulation of miR-802

Long noncoding RNAs (lncRNAs) present the key regulatory functions in tumorigenesis. More and more studies have suggested that lncRNA MIR155HG is involved in different human cancers. However, the underlying regulatory role of lncRNA MIR155HG and potential mechanisms in pancreatic cancer (PC) remain illusive. In this research, our group found that lncRNA MIR155HG expression was remarkably increased in PC tumor tissue and cells compared to that in the adjacent normal tissue and cells. In addition, higher MIR155HG expression was positively associated with the poor prognosis of patients. In addition, we exhibited that silence of MIR155HG by short hairpin RNA knockdown significantly inhibited cell growth and promoted cell apoptosis in PC cells. We performed bioinformatics analysis to search for the target of MIR155HG. As demonstrated by Luciferase reporter assay, we found that miR-802, a tumor suppressor in various cancer, is a direct target of MIR155HG. We demonstrated that the tumor-promoting effects of MIR155HG were contributed by negative regulation of miR-802 in PC cells. In summary, our results suggest that lncRNA MIR155HG might be applied as a novel diagnostic and therapeutic target for PC.     

Role of thrombin in the pathogenesis of atherosclerosis

Atherosclerosis is an arterial disease associated with inflammation. Thrombin is a procoagulant and proinflammatory serine protease that contributes to the pathology of atherosclerosis by enhancing the expression of cell adhesion molecules, inducing the secretion of proinflammatory cytokines, activating inflammatory responses in atherosclerotic plaques, stimulating proliferation of aortic smooth muscle cells, and exacerbating vascular lesions at sites of injury. Hence, thrombin appears to be an important target for treatment of atherosclerosis and thrombin pharmacological inhibitors have significant therapeutic potency for suppressing inflammatory responses in cardiovascular diseases. This review summarizes the proinflammatory signaling functions of thrombin as well as the therapeutic potency of thrombin inhibitors in the pathogenesis of atherosclerosis and hence their potential therapeutic value in this condition.     

miR-155对人椎间盘退变髓核细胞凋亡的作用及机制研究

目的:探讨mi R-155对人椎间盘退变髓核细胞凋亡的影响及其作用机制。方法:首先构建慢病毒表达载体,在293T细胞中获得重组慢病毒,然后感染椎间盘退变髓核细胞得到稳定过表达细胞系,同时设置空载体和空白细胞组对照。用荧光显微镜观察慢病毒载体的标签蛋白GFP的表达,分别提取三组细胞总RNA,采用RT-q PCR方法检测mi R-155的表达;通过流式细胞术检测细胞凋亡,Western-Blot检测细胞中凋亡相关蛋白FADD、Caspase-3、Bcl-2及Bax的表达,JC-1试剂盒检测细胞线粒体膜电位的变化情况。结果:在荧光显微镜下,经慢病毒感染的过表达细胞系和空载体细胞系均出现绿色荧光,而空白细胞组未见绿色荧光;RT-qPCR结果显示构建的稳定过表达细胞系(GV369-miR-155-NP)中mi R-155的表达水平较高,且与空载体细胞系及空白细胞对照组均呈显著性差异(P0.05);与空载体组(GV369-NP)及空白细胞对照组相比,过表达组(GV369-miR-155-NP)细胞凋亡率显著降低(P0.05),FADD、Caspase-3、Bax的表达水平均明显下降,而Bcl-2表达水平显著增加(P0.05)。结论:mi R-155可能通过靶向结合Caspase-3和FADD阻止FasL-Fas途径或通过线粒体途径抑制人椎间盘退变髓核细胞凋亡。     

Exploring the mechanism of ellagic acid against gastric cancer based on bioinformatics analysis and network pharmacology

Ellagic acid (EA) is a natural polyphenolic compound. Recent studies have shown that EA has potential anticancer properties against gastric cancer (GC). This study aims to reveal the potential targets and mechanisms of EA against GC. This study adopted methods of bioinformatics analysis and network pharmacology, including the weighted gene co-expression network analysis (WGCNA), construction of protein–protein interaction (PPI) network, receiver operating characteristic (ROC) and Kaplan–Meier (KM) survival curve analysis, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics simulations (MDS). A total of 540 EA targets were obtained. Through WGCNA, we obtained a total of 2914 GC clinical module genes, combined with the disease database for screening, a total of 606 GC-related targets and 79 intersection targets of EA and GC were obtained by constructing Venn diagram. PPI network was constructed to identify 14 core candidate targets; TP53, JUN, CASP3, HSP90AA1, VEGFA, HRAS, CDH1, MAPK3, CDKN1A, SRC, CYCS, BCL2L1 and CDK4 were identified as the key targets of EA regulation of GC by ROC and KM curve analysis. The enrichment analysis of GO and KEGG pathways of key targets was performed, and they were mainly enriched in p53 signalling pathway, PI3K-Akt signalling pathway. The results of molecular docking and MDS showed that EA could effectively bind to 13 key targets to form stable protein–ligand complexes. This study revealed the key targets and molecular mechanisms of EA against GC and provided a theoretical basis for further study of the pharmacological mechanism of EA against GC.