Construction and Investigation of a lncRNA-Associated ceRNA Regulatory Network in Cholangiocarcinoma
Construction and Investigation of a lncRNA-Associated ceRNA Regulatory Network in Cholangiocarcinoma
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DOI：
10.3389/fonc.2019.00649
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发表时间：
2019-08-09
影响因子：
4.7
通讯作者：
Zhao, Haitao
中科院分区：
文献类型：
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作者：
Long, Junyu;Xiong, Jianping;Zhao, Haitao
背景/目的：胆管癌（CCA）作为一种常见于胆管的恶性肿瘤，预后较差。长非编码RNA（lncRNA）最近引起了越来越多的关注，因为它作为竞争性内源RNA（ceRNA）发挥作用，阻碍参与肿瘤转录后调控网络的miRNA功能。因此，为了探讨CCA的癌变机制并提高治疗效率，本研究对包括lncRNA、miRNA和mRNA数据在内的表达谱数据进行了全面的整合和分析。方法：对来自癌症基因组图谱（TOGA）数据库的36个CCA样本和9个正常样本的RNA测序和miRNA谱数据进行全面比较。然后，利用四个公共数据库建立了失调的lncRNA相关ceRNA网络。结果：综上所述，1,410个lncRNA、64个miRNA和3,494个mRNA作为CCA中异常表达的基因出现。然后，构建了与lncRNA相关的失调的ceRNA网络。该网络包括 116 个 lncRNA、13 个 miRNA 和 60 个 CCA 特异性 mRNA。生存分析显示，其中26个lncRNA、3个miRNA和13个mRNA是CCA患者的预后生物标志物。最后，选择了三个 mRNA 来验证它们在基因表达综合 (GEO) 数据库中的表达水平。结果表明，这些基因的表达在TOGA和GEO数据库之间高度一致。结论：本研究的结果提供了更好地了解CCA生物学中涉及的ceRNA网络，为改善CCA诊断和预后奠定了坚实的基础。
Background/Aims: As a type of malignant tumor commonly found in the bile duct, cholangiocarcinoma (CCA) has a poor prognosis. Long non-coding RNA (lncRNA) has recently drawn increasing attention because it functions as a competing endogenous RNA (ceRNA) to hinder miRNA functions that participate in posttranscriptional regulatory networks in tumors. Therefore, to investigate the mechanisms of CCA carcinogenesis and to enhance treatment efficiency, the expression profiles, including lncRNA, miRNA, and mRNA data, were comprehensively integrated and analyzed in this study.Methods: A comprehensive comparison was performed on the RNA-sequencing and miRNA profiles data of 36 CCA samples and 9 normal samples from The Cancer Genome Atlas (TOGA) database. Then, a dysregulated lncRNA-related ceRNA network was established by using four public databases.Results: In summary, 1,410 lncRNAs, 64 miRNAs, and 3,494 mRNAs appeared as genes that were aberrantly expressed in CCA. Then, a dysregulated ceRNA network related to the lncRNAs was constructed. The network included 116 lncRNAs, 13 miRNAs and 60 mRNAs specific to CCA. The survival analysis showed that, among them, 26 lncRNAs, 3 miRNAs, and 13 mRNAs were prognostic biomarkers for patients with CCA. Finally, three mRNAs were selected for validation of their expression levels in the Gene Expression Omnibus (GEO) database. The results indicated that the expression of those genes was highly consistent between the TOGA and GEO databases.Conclusions: The findings in this study provide a better understanding of the ceRNA network involved in CCA biology and lay a solid foundation for improving CCA diagnosis and prognosis.