Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Cell Biochem. 2019 Nov;120(11):18995-19003. doi: 10.1002/jcb.29222. Epub 2019 Jul 3.
Cholangiocarcinoma (CCA) is the second widespread liver tumor with relatively poor survival. Increasing evidence in recent studies showed long noncoding RNAs (lncRNAs) exert a crucial impact on the development and progression of CCA based on the mechanism of competing endogenous RNAs (ceRNAs). However, functional roles and regulatory mechanisms of lncRNA-regulated ceRNA in CCA, are only partially understood. The expression profile of messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs) downloaded from The Cancer Genome Atlas were comprehensively investigated. Differential expression of these three types of RNA between CCA and corresponding precancerous tissues were screened out for further analysis. On the basis of interactive information generated from miRDB, miRTarBase, TargetScan, and miRcode public databases, we then constructed an mRNA-miRNA-lncRNA regulatory network. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were conducted to identify the biological function of the ceRNA network involved in CCA. As a result, 2883 mRNAs, 136 miRNAs, and 993 lncRNAs were screened out as differentially expressed RNAs in CCA. In addition, a ceRNA network in CCA was constructed, composing of 50 up and 27 downregulated lncRNAs, 14 up and 7 downregulated miRNAs, 29 up and 25 downregulated mRNAs. Finally, gene set enrichment and pathway analysis indicated our CCA-specific ceRNA network was related with cancer-related pathway and molecular function. In conclusion, our research identified a novel lncRNA-related ceRNA network in CCA, which might act as a potential therapeutic target for patients with CCA.
胆管癌（CCA）是第二大常见的肝脏肿瘤，其生存率相对较差。最近的研究越来越多的证据表明，长链非编码 RNA（lncRNA）基于竞争内源性 RNA（ceRNA）的机制，对 CCA 的发展和进展有重要影响。然而，lncRNA 调控的 ceRNA 在 CCA 中的功能作用和调控机制仍部分未知。从癌症基因组图谱下载信使 RNA（mRNA）、长链非编码 RNA（lncRNA）和 microRNA（miRNA）的表达谱进行综合研究。筛选出 CCA 和相应癌前组织之间这三种 RNA 的差异表达，进行进一步分析。基于 miRDB、miRTarBase、TargetScan 和 miRcode 公共数据库生成的交互信息，我们构建了一个 mRNA-miRNA-lncRNA 调控网络。京都基因与基因组百科全书和基因本体论分析用于识别涉及 CCA 的 ceRNA 网络的生物学功能。结果筛选出 2883 个 mRNAs、136 个 miRNAs 和 993 个 lncRNAs 作为 CCA 中的差异表达 RNA。此外，构建了一个 CCA 中的 ceRNA 网络，由 50 个上调和 27 个下调的 lncRNA、14 个上调和 7 个下调的 miRNA、29 个上调和 25 个下调的 mRNA 组成。最后，基因集富集和通路分析表明，我们的 CCA 特异性 ceRNA 网络与癌症相关通路和分子功能有关。总之，我们的研究确定了 CCA 中一个新的 lncRNA 相关 ceRNA 网络，它可能成为 CCA 患者的潜在治疗靶点。
