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肝细胞癌中关键基因、微小RNA和长链非编码RNA的综合分析

Comprehensive analysis of key genes, microRNAs and long non-coding RNAs in hepatocellular carcinoma.

作者信息

Shi Baoqi, Zhang Xuejun, Chao Lumeng, Zheng Yu, Tan Yongsheng, Wang Liang, Zhang Wei

机构信息

Department of Intervention Inner Mongolia People's Hospital Hohhot China.

出版信息

FEBS Open Bio. 2018 Jul 31;8(9):1424-1436. doi: 10.1002/2211-5463.12483. eCollection 2018 Sep.

DOI:10.1002/2211-5463.12483
PMID:30186744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6120244/
Abstract

Human hepatocellular carcinoma (HCC) is a common aggressive cancer whose molecular mechanism remains elusive. We aimed to identify the key genes, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) involved with HCC. We obtained mRNA, miRNA and lncRNA profiles for HCC from The Cancer Genome Atlas and then identified differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs). We performed functional annotation of DEmRNAs and then constructed HCC-specific DEmiRNA-DEmRNA, DEmiRNA-DElncRNA and DElncRNA-DEmiRNA-DEmRNA interaction networks. We searched for nearby target -DEmRNAs of DElncRNAs and performed receiver operating characteristic and survival analyses. A total of 1239 DEmRNAs, 33 DEmiRNAs and 167 DElncRNAs in HCC were obtained. Retinol metabolism [false discovery rate (FDR) = 7.02 × 10] and metabolism of xenobiotics by cytochrome P450 (FDR = 7.30 × 10) were two significantly enriched pathways in HCC. We obtained 545 DEmiRNA-DEmRNA pairs that consisted of 258 DEmRNAs and 28 DEmiRNAs in HCC. mir-424, miR-93 and miR-3607 are three hub DEmiRNAs of the HCC-specific DEmiRNA-DEmRNA interaction network. HAND2-AS1/ENSG00000232855-miR-93-, ENSG00000232855-miR-877- and ENSG00000232855-miR-224- interactions were found in the HCC-specific DElncRNA-DEmiRNA-DEmRNA interaction network. A total of three DElncRNA-nearby target DEmRNA pairs (HCG25-, LOC105378687- and LOC101927043-) in HCC were obtained. Diagnostic and prognostic values of several selected DElncRNAs, DEmRNAs and DEmiRNAs for HCC were assessed. Our study identified several DEmRNAs, DEmiRNAs and DElncRNAs with great diagnostic or prognostic value for HCC, which may facilitate studies into the molecular mechanisms, and development of potential biomarkers and therapeutic target sites for HCC.

摘要

人类肝细胞癌(HCC)是一种常见的侵袭性癌症,其分子机制仍不清楚。我们旨在鉴定与HCC相关的关键基因、微小RNA(miRNA)和长链非编码RNA(lncRNA)。我们从癌症基因组图谱中获取了HCC的mRNA、miRNA和lncRNA谱,然后鉴定了差异表达的mRNA(DEmRNA)、miRNA(DEmiRNA)和lncRNA(DElncRNA)。我们对DEmRNA进行了功能注释,然后构建了HCC特异性的DEmiRNA-DEmRNA、DEmiRNA-DElncRNA和DElncRNA-DEmiRNA-DEmRNA相互作用网络。我们搜索了DElncRNA的附近靶标DEmRNA,并进行了受试者工作特征分析和生存分析。在HCC中总共获得了1239个DEmRNA、33个DEmiRNA和167个DElncRNA。视黄醇代谢[错误发现率(FDR)=7.02×10]和细胞色素P450对外源生物的代谢(FDR=7.30×10)是HCC中两个显著富集的途径。我们在HCC中获得了545对DEmiRNA-DEmRNA,由258个DEmRNA和28个DEmiRNA组成。mir-424、miR-93和miR-3607是HCC特异性DEmiRNA-DEmRNA相互作用网络的三个枢纽DEmiRNA。在HCC特异性DElncRNA-DEmiRNA-DEmRNA相互作用网络中发现了HAND2-AS1/ENSG00000232855-miR-93-、ENSG00000232855-miR-877-和ENSG00000232855-miR-224-相互作用。在HCC中总共获得了三对DElncRNA附近靶标DEmRNA(HCG25-、LOC105378687-和LOC101927043-)。评估了几种选定的DElncRNA、DEmRNA和DEmiRNA对HCC的诊断和预后价值。我们的研究鉴定了几种对HCC具有重要诊断或预后价值的DEmRNA、DEmiRNA和DElncRNA,这可能有助于对分子机制的研究,以及HCC潜在生物标志物和治疗靶点的开发。

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