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基于竞争内源性 RNA 的宫颈癌中异常 lncRNA-miRNA-mRNA 网络的构建与分析。

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

机构信息

Department of Oral and Maxillofacial Surgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China.

Department of Clinical Laboratory, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China.

出版信息

J Cell Biochem. 2018 Aug;119(8):6665-6673. doi: 10.1002/jcb.26850. Epub 2018 May 9.

DOI:10.1002/jcb.26850
PMID:29741786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6055788/
Abstract

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.

摘要

越来越多的研究表明,长链非编码 RNA(lncRNA)被认为是 ceRNA 网络的主要组成部分。这是因为它可以作为 miRNA 的海绵来调节蛋白质编码基因的表达。然而,lncRNA 介导的 ceRNA 在宫颈鳞状细胞癌(CESC)中的功能作用和调控机制,以及它们在预测 CESC 预后方面的潜在应用,仍然未知。从 TCGA 数据库中获得了 306 例宫颈鳞状癌组织和 3 例相邻宫颈组织的 mRNA、lncRNA 和 miRNA 的异常表达谱。构建了 CESC 的 lncRNA-mRNA-miRNA ceRNA 网络。同时,使用 Cytoscape 插件 BinGo 和 DAVID 数据库对基因本体论(GO)和 KEGG 通路进行分析。我们总共鉴定出 493 个 lncRNA、70 个 miRNA 和 1921 个 mRNA 作为差异表达谱。在 CESC 中构建了一个异常的 lncRNA-mRNA-miRNA ceRNA 网络,它由 50 个 DElncRNA、18 个 DEmiRNA 和 81 个 DEmRNA 组成。根据总体生存分析,50 个 lncRNA 中有 3 个、81 个 mRNA 中有 10 个和 18 个 miRNA 中有 1 个作为 CESC 患者的预后生物标志物(P 值<0.05)。我们从 ceRNA 网络中提取了子网络,发现两个新的 lncRNA 被认为是关键基因。它们包括 lncRNA MEG3 和 lncRNA ADAMTS9-AS2。本研究为更好地理解 CESC 中 lncRNA 相关 ceRNA 网络提供了新的视角,新识别的 ceRNA 网络将有助于我们更好地理解 lncRNA 介导的 ceRNA 在 CESC 发病机制中的调控机制。

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