长链非编码RNA在动脉粥样硬化中的研究进展

动脉粥样硬化(As)是一种复杂的慢性疾病,其特征在于血管壁中的脂质沉积,涉及到主要功能细胞,包括平滑肌细胞、内皮细胞和免疫细胞的炎性和增殖性级联反应。目前,As机制的认知以及动脉粥样硬化性心血管疾病(ASCVD)的治疗有了实质性的改善,但疾病死亡率以及经济负担仍然很高。长链非编码基因(lncRNA)是一种不具有编码蛋白质功能的转录产物,广泛参与细胞发育、增殖、分化、凋亡等生物学功能的调节。在肿瘤、神经系统疾病等研究领域,已被作为重要的生物标记物以及治疗靶点被广泛研究。同时,大量证据表明在As的调节通路中lncRNAs同样发挥着重要的作用,不仅更全面地阐述了As发生发展机制,也为开发新型诊断标记物和治疗方法提供了新的方向。     

长链非编码RNA作为ceRNA在结直肠癌中的作用

结直肠癌(colorectal cancer,CRC)是全球第三大恶性肿瘤,恶性程度高,具有很高的转移和复发率.长链非编码RNA(lncRNA)在CRC发生发展过程中发挥重要作用.最近的研究表明,lncRNA可通过与微小RNA(miRNA)的反应元件(MRE)结合,充当竞争性内源RNA(ceRNA),从而间接调控miR...     

动脉粥样硬化相关循环血长链非编码RNA研究进展

动脉粥样硬化(As)是最常见的心脑血管疾病病变,严重影响着现代社会人类的身体健康。在As复杂的病理变化过程中寻找潜在的生物标记物,对于预防和治疗As疾病的发生和发展有着重要意义。研究表明长链非编码RNA(lncRNA)能够广泛参与到多种细胞活性的调控过程中,在As发生发展的不同阶段发挥作用。lncRNA可经由外泌体、微囊泡以及凋亡小体的包被,分泌至胞外后,进入循环系统。近些年,陆续有关于循环血lncRNA与As发生发展相关性的研究,血液中的lncRNA有望成为监测As病情进展的新型非介入诊断标记物。     

小鼠高脂血症模型的竞争性内源RNA调控网络研究

目的基于高通量测序数据,探讨小鼠高脂血症模型中长链非编码RNA(long non-coding RNA,lncRNA)的表达特征及竞争性内源RNA(competitive endogenous RNA,ceRNA)调控网络,筛选lncRNA介导的参与血脂异常发生发展的关键调控通路。方法应用正常饮食和高脂饮食分别诱导ApoE-/-小鼠12周,建立高脂血症模型;进行肝脏全转录组测序,筛选差异表达的lncRNAs、微小RNAs(microRNAs,miRNAs)和信使RNAs(messenger RNAs,mRNAs);对差异表达的mRNAs进行基因功能(Gene Ontology,GO)分析和信号通路(KEGG)注释;结合并分析lncRNA-mRNA共表达关系、miRNA-mRNA靶向关系、lncRNA-miRNA共表达和靶向关系,构建lncRNA介导的ceRNA网络并筛选关键ceRNA调控轴。结果高脂血症小鼠肝脏全转录组测序筛选出117个差异表达lncRNAs、53个差异表达miRNAs和1689个差异表达mRNAs;差异表达的mRNAs主要参与脂质代谢过程、脂肪酸代谢过程和类固醇代谢过程等生物学功能,涉及PPAR信号通路和不饱和脂肪酸合成等途径;构建的ceRNA调控网络包括16个lncRNAs节点、18个miRNAs节点和33个mRNAs节点,其中lnc-Dubr介导的ceRNA调控轴可能对血脂异常具有重要调控作用。结论成功绘制出高脂血症小鼠肝脏lncRNA介导的ceRNA调控网络,并筛选出具有潜在生物学作用的ceRNA调控轴,有望为高脂血症及其他心血管疾病的发生发展和治疗提供新的线索和思路。     

长链非编码RNA在胃肠道疾病中的研究进展

长链非编码RNA(long noncoding RNA,lncRNA)是一类转录本长度超过200个核苷酸,具有调控基因表达但不表现任何蛋白质编码潜能的非编码RNA(non-coding RNA,ncRNA),在总ncRNA中占有相当大的比例,目前已成为继microRNA之后又一研究的新热点。lncRNA广泛参与机体几乎所有的生理和病理过程,尤其通过表观遗传调控等方式参与并影响肿瘤细胞的生长、凋亡、浸润与转移等过程,它在肿瘤诊断和治疗方面已显示出良好的临床应用前景,有望成为新型肿瘤标志物和肿瘤治疗的新靶点。本文就lncRNA在胃肠道常见疾病中的研究进展作一概述。     

大鼠颈动脉球囊损伤模型的竞争性内源RNA调控网络研究

目的构建大鼠颈动脉球囊损伤模型的竞争性内源RNA(competing endogenous RNA,ceRNA)调控网络,筛选血管新生内膜形成中的关键调控基因。方法首先建立大鼠颈动脉球囊损伤模型。将12只SD大鼠随机分为2组(每组6只):手术组,利用2F取栓球囊于左颈总动脉行球囊损伤术;假手术组:夹闭左颈总动脉,使血流阻断时间接近球囊损伤术操作时间。术后14 d取颈总动脉血管组织,提取总RNA,进行长链非编码RNA(long non-coding RNA,lncRNA)和信使mRNA(messenger RNA,mRNA)测序。应用生物信息学方法进行差异表达lncRNA和mRNA共表达分析、基因功能(Gene Ontology,GO)和信号通路(Pathway)分析;通过数据库预测微小RNA(microRNA,miRNA)与lncRNA及mRNA的结合关系,并从中筛选已报道在大鼠血管内膜增生过程中有生物学功能的miRNA相关的结合关系,得到最终的ceRNA网络。结果与假手术组相比,手术组鉴定出1731个差异表达的mRNAs和99个差异表达的lncRNAs;GO和Pathway分析显示,差异表达的mRNA主要参与调节免疫反应、细胞迁移、细胞黏附等。ceRNA分析构建了由46个mRNAs、18个lncRNAs和16个miRNAs组成的ceRNA网络,其中AABR07073245.1、Col6a3、AABR07071659.2和AABR07067310.2所介导的ceRNA调控轴可能在大鼠血管新生内膜形成中具有重要调控作用。结论本研究系统分析大鼠颈动脉球囊损伤模型表达谱,构建的ceRNA调控网络可能在大鼠血管内膜增生过程中具有重要调控作用,有望为动脉粥样硬化的防治提供新的靶点与分子标志物。     

长链非编码RNA与肿瘤的研究进展

<正>中心法则认为遗传信息被储存在能够编码蛋白质的基因中〔1〕,长链非编码RNA是一种长度大于200个核苷酸、但不具备编码蛋白质功能的基因转录产物〔2~4〕。先前的大部分研究仅仅发现非编码RNA(ncRNA)拥有一些结构功能,但近些年来RNA领域的一些研究开始挑战先前对ncRNA的一些认识〔3,5~11〕,LncRNA在肿瘤发生、发展过程中起到重要作用。     

长链非编码RNA在血管生成中的研究进展

生理性的血管生成对于组织修复、机体平衡具有重要的作用,但异常的血管生成可诱发多种疾病,如癌症、缺血性心脏病、中风等。调节血管的生成对于诸多疾病的治疗具有重要意义,抗血管生成疗法已在某些疾病中显示了治疗意义,但促血管生成疗法仍然是一个难题。近年来,大量研究显示长链非编码RNA(lncRNA)在血管生成中扮演着重要的角色,通过调节异常的lncRNA,可以抑制或促进血管生成,这为治疗异常血管生成的相关疾病开辟了新的领域。     

Construction and comprehensive analysis of a competitive endogenous RNA network to reveal potential biomarkers for the malignant differentiation of glioma

Background:Long noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression; therefore, lncRNAs are considered major components of the competitive endogenous RNA (ceRNA) network and have attracted growing attention. This study explored the regulatory mechanisms and functional roles of lncRNAs as ceRNAs in the malignant differentiation of low-grade glioma (LGG) to glioblastoma (GBM) and their potential impact on the prognosis of patients with GBM.Methods:LncRNA and messenger RNA (mRNA) data were extracted from the Cancer Genome Atlas (TCGA) database from 156 GBM samples and 529 LGG samples. Separately, the miRNA expression data were downloaded from the Gene Expression Omnibus database, with the {"type":"entrez-geo","attrs":{"text":"GSE112009","term_id":"112009"}}GSE112009 dataset containing miRNA expression data from 10 GBM samples and 15 LGG samples. Weighted gene coexpression network analysis was performed to screen the glioma grade-related lncRNAs. Then, a ceRNA network was established. The database for annotation, visualization, and integrated discovery was adopted to conduct functional enrichment analysis based on 57 upregulated differentially expressed mRNAs in the ceRNA network. Finally, Kaplan–Meier curves were created for the survival analysis of 13 hub lncRNA by combining the clinical data of GBM patients in TCGA.Results:A ceRNA network including 16 lncRNAs, 18 miRNAs, and 78 mRNAs specific to the malignant differentiation of LGG to GBM was established. The 57 upregulated differentially expressed mRNAs in the ceRNA network were significantly enriched in 35 gene ontology terms and 5 pathways. The survival analysis showed that 2 lncRNAs (LINC00261 and HOXA10-AS) were prognostic biomarkers for patients with GBM in TCGA.Conclusion:The proposed ceRNA network may help elucidate the regulatory mechanism by which lncRNAs function as ceRNAs and contribute to the malignant differentiation of LGG to GBM. Importantly, the candidate lncRNAs, miRNAs, and mRNAs involved in the ceRNA network can be further evaluated as potential therapeutic targets and prognostic biomarkers for GBM.     

Role of long noncoding RNA-mediated competing endogenous RNA regulatory network in hepatocellular carcinoma

Long noncoding RNAs(lnc RNAs) and micro RNAs(mi RNAs) are noncoding RNAs(nc RNAs) that occupy over 90% of the human genome, and their main function is to directly or indirectly regulate messenger RNA(m RNA) expression and participate in the tumorigenesis and progression of malignances. In particular, some lnc RNAs can interact with mi RNAs as competing endogenous RNAs(ce RNAs) to modulate m RNA expression. Accordingly, these RNA molecules are interrelated and coordinate to form a dynamic lnc RNA-mediated ce RNA regulatory network. Mounting evidence has revealed that lnc RNAs that act as ce RNAs are closely related to tumorigenesis. To date, numerous studies have established many different regulatory networks in hepatocellular carcinoma(HCC), and perturbations in these ce RNA interactions may result in the initiation and progression of HCC. Herein, we emphasize recent advances concerning the biological function of lnc RNAs as ce RNAs in HCC, with the aim of elucidating the molecular mechanism underlying these HCC-related RNA molecules and providing novel insights into the diagnosis and treatment of HCC.     

血清长链非编码RNA n342721在急性心肌梗死患者中的表达及意义

目的 探索一种新的长链非编码RNA n342721(lncRNA n342721)在急性心肌梗死(AMI)患者血清中的表达及临床意义.方法 采用人类全转录组芯片2.0技术在5例AMI患者和5例非冠心病(non-CHD)者血清检测lncRNA的表达,筛选出表达水平差异明显的6个上调lncRNA;并在20例AMI患者和20...     

Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer

AIM To investigate the role of long noncoding RNA(lnc RNA) RP4 in colorectal cancer.METHODS Lentivirus-mediated lnc RNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an in vivo xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lnc RNA RP4 mechanism involved assessment of the association of its expression with mi R-7-5 p and the SH3 GLB1 gene. Western blot analysis was also performed to assess the effect of lnc RNA RP4 on the autophagy-mediated cell death pathway and phosphatidylinositol-3-kinase(PI3 K)/Akt signaling.RESULTS Cell proliferation, tumor growth, and early apoptosis in SW480 cells were negatively regulated by lnc RNA RP4. Functional experiments indicated that lnc RNA RP4 directly upregulated SH3 GLB1 expression by acting as a competing endogenous RNA(ce RNA) for mi R-7-5 p. This interaction led to activation of the autophagy-mediated cell death pathway and de-repression of PI3 K and Akt phosphorylation in colorectal cancer cells in vivo.CONCLUSION Our results demonstrated that lnc RNA RP4 is a ce RNA that plays an important role in the pathogenesis of colorectal cancer, and could be a potential therapeutic target for colorectal cancer treatment.