长链非编码RNA在动脉粥样硬化中的作用

动脉粥样硬化是一种致病因素多样、病理机制复杂的心血管疾病。近年研究发现,长链非编码RNA在动脉粥样硬化的发生、发展过程中发挥重要的调控作用。通过调节脂代谢、糖尿病、肥胖等危险因素,参与血管内皮功能、血管新生、免疫炎症等病理机制,影响动脉粥样硬化的疾病进程。本文就长链非编码RNA在动脉粥样硬化中的研究现状,综述其对疾病危险因素及病理机制的调控作用。     

长链非编码 RNA 在心肌生理和病理生理功能调控中的作用

长链非编码RNA(long non-coding RNA,lncRNA)是一组超过200个核苷酸的非编码转录RNA,能与DNA或RNA、miRNA结合位点和启动子的靶碱基结合,改变基因表达,或者直接调节蛋白功能,参与胚胎发生发育、器官功能稳态维持以及疾病发生发展等多种生理和病理过程。近年多项研究结果表明,lncRNA不但在生理性心脏发生发育、心脏各类型细胞分化和转化过程发挥重要作用,而且在心脏疾病,如心肌肥厚、心力衰竭、心肌梗死和心脏缺血再灌注损伤等病理性疾病中,表达谱发生动态改变。     

长链非编码RNA在心肌生理和病理生理功能调控中的作用北大核心CSCD

长链非编码RNA(long non-coding RNA,lncRNA)是一组超过200个核苷酸的非编码转录RNA,能与DNA或RNA、miRNA结合位点和启动子的靶碱基结合,改变基因表达,或者直接调节蛋白功能,参与胚胎发生发育、器官功能稳态维持以及疾病发生发展等多种生理和病理过程。近年多项研究结果表明,lncRNA不但在生理性心脏发生发育、心脏各类型细胞分化和转化过程发挥重要作用,而且在心脏疾病,如心肌肥厚、心力衰竭、心肌梗死和心脏缺血再灌注损伤等病理性疾病中,表达谱发生动态改变。     

长链非编码RNA与缺血缺氧性疾病的研究进展

长链非编码RNA(long non-coding RNA,lnc RNA)是指转录本长度超过200 nt的不编码蛋白质的RNA。lnc RNA在细胞增殖分化、个体发育、干细胞活性与代谢等几乎所有重要生命活动中发挥关键的调控作用,与多种疾病的发生密切相关。近年研究表明,lnc RNA在多种器官缺血缺氧的发生及恢复中发挥着重要的作用。现探讨lnc RNA在缺血缺氧性疾病中的调控机制,重点介绍lnc RNA与缺血性脑卒中和缺血性心脏病的关系,以期为缺血缺氧相关心脑血管疾病的早期预防、诊断和治疗提供新策略。     

microRNA与心脏疾病

microRNA是植物和动物基因组编码的小分子非编码RNA.这种高度保守、长21～25个碱基RNA分子通过与mRNA的3'非编码区结合来调控基因组表达.microRNA通过其转录后调控机制在胚胎发育、细胞增殖,细胞分化、细胞死亡及细胞凋亡中发挥调控作用.近期研究发现,microRNA的异常表达可导致心脏疾病的发生、发展.现对microRNA在心脏发育、心肌肥厚和心肌重构、心力衰竭和心律失常等过程中的作用进行综述.     

非编码RNA在心脏稳态维持中的功能和机制

心脏的稳态维持依赖动态重塑来实现。心脏重塑异常是多种心血管疾病的主要病理生理基础,它能引起心肌肥厚、间质纤维化和心脏功能受损等结构和功能的改变,并最终导致心力衰竭。非编码RNA(ncRNA)是指不编码蛋白质的RNA分子。微小RNA (miRNA)和长链非编码RNA (lncRNA)是非编码RNA的两种主要类型,在基因转录、RNA成熟和蛋白质翻译等水平调控基因表达,参与许多重要的生命过程。近年来的研究表明,这两种非编码RNA参与心脏重塑和心脏疾病发生。该文将介绍miRNA和lncRNA在心脏稳态维持中功能及其机制的最新研究进展,以及它们作为心脏疾病诊断分子标志物及治疗靶标的前景。     

线粒体miRNA及其生物学功能

线粒体是细胞中重要的细胞器,是机体主要的能量代谢场所,参与调节机体的多项生命活动,线粒体功能异常与多种疾病的发生、发展密切相关。微小RNA(micro RNA,miRNA)是一类由内源基因编码的长度为20~25个核苷酸的非编码单链RNA分子,广泛存在于真核生物中。研究表明,miRNA通过抑制靶信使RNA(messenger RNA,m RNA)翻译或促进其降解,在转录后水平调控基因表达。近三分之一的编码基因受miRNA调控,miRNA几乎参与了机体所有的生命活动。以往的研究主要集中于miRNA在细胞核及细胞质中的功能,近年来关于miRNA在线粒体中发挥作用的报道越来越多,miRNA已成为当今生物学研究的新热点。线粒体miRNA对线粒体的功能具有重要的调控作用,并参与许多疾病的发生、发展。该文将就线粒体miRNA及其生物学功能作一综述。     

长链非编码RNA在心脏疾病中的作用

长链非编码RNA(long non-coding RNA,lnc RNA)在转录、转录后和表观遗传学水平调控基因表达,参与多种生物学过程。最近研究表明,lnc RNA在心脏疾病的发生和发展过程中扮演着关键角色。该文就lnc RNA在心脏发育与心脏疾病中的作用作一综述,并指出它具有重要的诊断和治疗潜能。     

miRNA在衣原体感染中的作用

衣原体是一种专性胞内寄生的原核细胞型微生物,是感染人和动物常见的病原体之一,能引起人类和动物罹患多种疾病。miRNA是一类内源性非编码单链RNA分子,在细胞的增殖与分化、自噬与凋亡、病毒感染等生理和病理过程中发挥重要作用。近年来相关研究发现,衣原体感染后能引起宿主的miRNA表达水平发生改变,其不仅调节宿主细胞线粒体网络结构进而影响衣原体的生长发育,还作为区分不同衣原体变体引起感染的早期生物标志物。miRNA参与了衣原体感染过程的调控,但miRNA在衣原体感染中的作用机制尚不完全清楚。本文就miRNA在衣原体感染中的作用进行简要综述。     

表观遗传学: 生物细胞非编码RNA调控的研究进展

表观遗传学是研究基因表达发生了可遗传的改变, 而DNA序列不发生改变的一门生物学分支, 对细胞的生长分化及肿瘤的发生发展至关重要。表观遗传学的主要机制包括DNA甲基化、组蛋白修饰及新近发现的非编码RNA。非编码RNA 是指不能翻译为蛋白的功能性RNA分子, 其中常见的具调控作用的非编码RNA包括小干涉RNA、miRNA、piRNA 以及长链非编码RNA。近年来大量研究表明非编码RNA在表观遗传学的调控中扮演了越来越重要的角色。文章综述了近年来生物细胞非编码RNA调控的表观遗传学研究进展, 以有助于理解哺乳动物细胞中非编码RNA及其调控机制和功能。     

A genome‐scale analysis of mRNAs targeting to plant mitochondria: upstream AUGs in 5' untranslated regions reduce mitochondrial association

Intracellular sorting of mRNAs is an essential process for regulating gene expression and protein localization. Most mitochondrial proteins are nuclear‐encoded and imported into the mitochondria through post‐translational or co‐translational processes. In the latter case, mRNAs are found to be enriched in the vicinity of mitochondria. A genome‐scale analysis of mRNAs associated with mitochondria has been performed to determine plant cytosolic mRNAs targeted to the mitochondrial surface. Many messengers encoding mitochondrial proteins were found associated with mitochondria. These mRNAs correspond to particular functions and complexes, such as respiration or mitoribosomes, which indicates a coordinated control of mRNA localization within metabolic pathways. In addition, upstream AUGs in 5' untranslated regions (UTRs), which modulate the translation efficiency of downstream sequences, were found to negatively affect the association of mRNAs with mitochondria. A mutational approach coupled with in vivo mRNA visualization confirmed this observation. Moreover, this technique allowed the identification of 3'‐UTRs as another essential element for mRNA localization at the mitochondrial surface. Therefore, this work offers new insights into the mechanism, function and regulation of the association of cytosolic mRNAs with plant mitochondria.     

Regulatory networks of non-coding RNAs in brown/beige adipogenesis

BAT (brown adipose tissue) is specialized to burn fatty acids for heat generation and energy expenditure to defend against cold and obesity. Accumulating studies have demonstrated that manipulation of BAT activity through various strategies can regulate metabolic homoeostasis and lead to a healthy phenotype. Two classes of ncRNA (non-coding RNA), miRNA and lncRNA (long non-coding RNA), play crucial roles in gene regulation during tissue development and remodelling. In the present review, we summarize recent findings on regulatory role of distinct ncRNAs in brown/beige adipocytes, and discuss how these ncRNA regulatory networks contribute to brown/beige fat development, differentiation and function. We suggest that targeting ncRNAs could be an attractive approach to enhance BAT activity for protecting the body against obesity and its pathological consequences.     

Identification of mitochondrial function‐associated lncRNAs in septic mice myocardium

The present study aimed to analyze long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in septic mice heart and to identify potential lncRNAs and mRNAs that be responsible for cardiac mitochondrial dysfunction during sepsis. Mice were treated with 10 mg/kg of lipopolysaccharides to induce sepsis. LncRNAs and mRNAs expression were evaluated by using lncRNA and mRNA microarray or real‐time polymerase chain reaction technique. LncRNA‐mRNA coexpression network assay, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. The results showed that 1275 lncRNAs were differentially expressed in septic myocardium compared with those in the control group. A total of 2769 mRNAs were dysregulated in septic mice heart, most of which are mainly related to the process of inflammation, mitochondrial metabolism, oxidative stress, and apoptosis. Coexpression network analysis showed that 14 lncRNAs were highly correlated with 11 mitochondria‐related differentially expressed mRNA. Among all lncRNAs and their cis‐acting mRNAs, 41 lncRNAs‐mRNA pairs (such as NONMMUG004378 and Apaf1 gene) were enriched in GO terms and KEGG pathways. In summary, we gained some specific lncRNAs and their potential target mRNAs that might be involved in mitochondrial dysfunction in septic myocardium. These findings provide a panoramic view of lncRNA and might allow developing new treatment strategies for sepsis.     

Integrative analysis of competing endogenous RNA networks reveals the functional lncRNAs in heart failure

Heart failure has become one of the top causes of death worldwide. It is increasing evidence that lncRNAs play important roles in the pathology processes of multiple cardiovascular diseases. Additionally, lncRNAs can function as ceRNAs by sponging miRNAs to affect the expression level of mRNAs, implicating in numerous biological processes. However, the functional roles and regulatory mechanisms of lncRNAs in heart failure are still unclear. In our study, we constructed a heart failure‐related lncRNA‐mRNA network by integrating probe re‐annotation pipeline and miRNA‐target interactions. Firstly, some lncRNAs that had the central topological features were found in the heart failure‐related lncRNA‐mRNA network. Then, the lncRNA‐associated functional modules were identified from the network, using bidirectional hierarchical clustering. Some lncRNAs that involved in modules were demonstrated to be enriched in many heart failure‐related pathways. To investigate the role of lncRNA‐associated ceRNA crosstalks in certain disease or physiological status, we further identified the lncRNA‐associated dysregulated ceRNA interactions. And we also performed a random walk algorithm to identify more heart failure‐related lncRNAs. All these lncRNAs were verified to show a strong diagnosis power for heart failure. These results will help us to understand the mechanism of lncRNAs in heart failure and provide novel lncRNAs as candidate diagnostic biomarkers or potential therapeutic targets.     

Reconstruction and analysis of the aberrant lncRNA‐miRNA‐mRNA network based on competitive endogenous RNA in CESC

A growing body of studies has demonstrated that long non‐coding RNA (lncRNA) are regarded as the primary section of the ceRNA network. This is thought to be the case owing to its regulation of protein‐coding gene expression by functioning as miRNA sponges. However, functional roles and regulatory mechanisms of lncRNA‐mediated ceRNA in cervical squamous cell carcinoma (CESC), as well as their use for potential prediction of CESC prognosis, remains unknown. The aberrant expression profiles of mRNA, lncRNA, and miRNA of 306 cervical squamous cancer tissues and three adjacent cervical tissues were obtained from the TCGA database. A lncRNA‐mRNA‐miRNA ceRNA network in CESC was constructed. Meanwhile, Gene Ontology (GO) and KEGG pathway analysis were performed using Cytoscape plug‐in BinGo and DAVID database. We identified a total of 493 lncRNA, 70 miRNA, and 1921 mRNA as differentially expressed profiles. An aberrant lncRNA‐mRNA‐miRNA ceRNA network was constructed in CESC, it was composed of 50 DElncRNA, 18 DEmiRNA, and 81 DEmRNA. According to the overall survival analysis, 3 out of 50 lncRNA, 10 out of 81 mRNA, and 1 out of 18 miRNA functioned as prognostic biomarkers for patients with CESC (P value < 0.05). We extracted the sub‐network in the ceRNA network and found that two novel lncRNA were recognized as key genes. These included lncRNA MEG3 and lncRNA ADAMTS9‐AS2. The present study provides a new insight into a better understanding of the lncRNA‐related ceRNA network in CESC, and the novel recognized ceRNA network will help us to improve our understanding of lncRNA‐mediated ceRNA regulatory mechanisms in the pathogenesis of CESC.