胆管癌中长非编码 RNA 相关竞争性内源性 RNA 网络的综合分析。
Comprehensive analysis of long noncoding RNA-associated competing endogenous RNA network in cholangiocarcinoma.
机构信息
Department of Intervention and Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou Cancer Medical Center, Suzhou, Jiangsu, 215001, China.
Department of Intervention and Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou Cancer Medical Center, Suzhou, Jiangsu, 215001, China.
出版信息
Biochem Biophys Res Commun. 2018 Dec 2;506(4):1004-1012. doi: 10.1016/j.bbrc.2018.10.186. Epub 2018 Nov 4.
BACKGROUND
Long non-coding RNAs (lncRNAs) can interact with microRNAs (miRNAs) as a competing endogenous RNA (ceRNA) to regulate the expression of target genes, which can largely influence on tumorigenesis and tumor progression. However, the role of lncRNA-mediated ceRNAs in cholangiocarcinoma (CCA) remains unknown. This study aimed to develop novel lncRNAs as well as their action mechanisms in CCA.
METHODS
The expression profiles of lncRNAs, miRNAs, and mRNAs of 36 CCA tissues and 9 non-tumor bile duct tissues were obtained from The Cancer Genome Atlas (TCGA) database. The differentially expressed RNAs werre identified using the DESeq package in R. The ceRNA network was constructed in CCA based on bioinformatics generated from miRcode, miRTarBase, miRDB, and TargetScan. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using "DAVID 6.8" and R packages "Clusterprofile". Survival analysis was performed based on Kaplan-Meier curve analysis.
RESULTS
We identified a total of 1411 differentially expressed lncRNAs, 3494 mRNAs, and 64 miRNAs between CCA and matched normal tissues. By combining the data predicted by databases with intersection RNAs, a lncRNA-miRNA-mRNA ceRNA network consisting of 116 lncRNAs, 14 miRNAs and 59 mRNAs was established. According to the survival analysis, we detected 11 DElncRNA to have a significant impact on the overall survival in patients with CCA (P < 0.05).
CONCLUSIONS
Our study identified novel lncRNAs associated with CCA progression and prognosis and provided data to further understand lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of CCA.
背景
长链非编码 RNA（lncRNA）可以作为竞争性内源性 RNA（ceRNA）与 microRNA（miRNA）相互作用，调节靶基因的表达，这在很大程度上影响肿瘤的发生和发展。然而，lncRNA 介导的 ceRNA 在胆管癌（CCA）中的作用尚不清楚。本研究旨在发现新的 lncRNA 及其在 CCA 中的作用机制。
方法
从癌症基因组图谱（TCGA）数据库中获取 36 例 CCA 组织和 9 例非肿瘤胆管组织的 lncRNA、miRNA 和 mRNA 表达谱。使用 R 中的 DESeq 包识别差异表达的 RNA。基于 miRcode、miRTarBase、miRDB 和 TargetScan 生成的生物信息学数据，在 CCA 中构建 ceRNA 网络。使用“DAVID 6.8”和 R 包“Clusterprofile”进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。基于 Kaplan-Meier 曲线分析进行生存分析。
结果
我们共鉴定出 1411 个在 CCA 与匹配正常组织之间差异表达的 lncRNA、3494 个 mRNA 和 64 个 miRNA。通过将数据库预测的数据与交集 RNA 相结合，构建了一个由 116 个 lncRNA、14 个 miRNA 和 59 个 mRNA 组成的 lncRNA-miRNA-mRNA ceRNA 网络。根据生存分析，我们检测到 11 个差异表达的 lncRNA 对 CCA 患者的总生存率有显著影响（P<0.05）。
结论
本研究鉴定出与 CCA 进展和预后相关的新型 lncRNA，并提供了数据来进一步了解 lncRNA 介导的 ceRNA 在 CCA 发病机制中的调控机制。
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