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胆管癌中异常表达的 lncRNAs、miRNAs 和 mRNAs 的综合分析及其相关 ceRNA 网络。

Comprehensive analysis of aberrantly expressed profiles of lncRNAs, miRNAs and mRNAs with associated ceRNA network in cholangiocarcinoma.

机构信息

Department of General Surgery, Second Hospital of He Fei Affiliated with Anhui Medical University, Hefei, Anhui, China.

Department of General Surgery, Anhui Provincial Hospital, Hefei, Anhui, China.

出版信息

Cancer Biomark. 2018;23(4):549-559. doi: 10.3233/CBM-181684.

Abstract

Cholangiocarcinoma (CCA) is a highly malignant and poorly differentiated bile duct cancer with an extremely poor prognosis, but the pathogenesis of CCA remains not well-known. Attention has been increasingly focused on long noncoding RNAs, which plays an important role in tumorigenesis. However, the roles of cancer specific lncRNA and its related competitive endogenous RNAs (ceRNA) network in CCA remain elusive. In this study, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 36 CCA tissues and 9 normal tissues in The Cancer Genome Atlas. 1434 cancer specific lncRNAs, 68 miRNAs and 3538 mRNAs (|logFC|> 1, p< 0.05) were identified. Based on bioinformatics generated from miRcode, starBase, miRTarBase, TargetScan and miRDB, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in CCA. We constructed the lncRNA-miRNA-mRNA ceRNA network consisting of 206 molecules and 454 interactions. In addition, we used Cytoscape software to visualize the ceRNA network in WGCNA, 22 mRNA network modules were identified, five of which were significantly related to tumor grade and survival time. Moreover, three lncRNAs COL18A1-AS1, SLC6A1-AS1 and HULC were found to be significantly associated with overall survival. The present study provides novel insight for better understanding of lncRNA-related ceRNA network in CCA and useful resource for identifcation of novel biomarkers of CCA.

摘要

胆管癌(CCA)是一种高度恶性和低分化的胆管癌,预后极差,但 CCA 的发病机制尚不清楚。人们越来越关注长非编码 RNA,它在肿瘤发生中起着重要作用。然而,CCA 中癌症特异性 lncRNA 及其相关竞争性内源性 RNA(ceRNA)网络的作用仍不清楚。在这项研究中,我们综合整合了来自 36 个 CCA 组织和 9 个正常组织的表达谱数据,包括 mRNA、lncRNA 和 miRNA。鉴定了 1434 个癌症特异性 lncRNA、68 个 miRNA 和 3538 个 mRNA(|logFC|>1,p<0.05)。基于从 miRcode、starBase、miRTarBase、TargetScan 和 miRDB 生成的生物信息学,我们构建了 CCA 中的 lncRNA-miRNA-mRNA 网络(ceRNA 网络)。我们构建了由 206 个分子和 454 个相互作用组成的 lncRNA-miRNA-mRNA ceRNA 网络。此外,我们使用 Cytoscape 软件在 WGCNA 中可视化 ceRNA 网络,鉴定出 22 个 mRNA 网络模块,其中 5 个与肿瘤分级和生存时间显著相关。此外,发现三个 lncRNA COL18A1-AS1、SLC6A1-AS1 和 HULC 与总生存期显著相关。本研究为更好地理解 CCA 中 lncRNA 相关 ceRNA 网络提供了新的见解,并为 CCA 新型生物标志物的鉴定提供了有用的资源。

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