Long Junyu, Xiong Jianping, Bai Yi, Mao Jinzhu, Lin Jianzhen, Xu Weiyu, Zhang Hui, Chen Shuguang, Zhao Haitao
Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Front Oncol. 2019 Aug 9;9:649. doi: 10.3389/fonc.2019.00649. eCollection 2019.
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. 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 (TCGA) database. Then, a dysregulated lncRNA-related ceRNA network was established by using four public databases. 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 TCGA and GEO databases. 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.
胆管癌（CCA）作为一种常见于胆管的恶性肿瘤，预后较差。长链非编码RNA（lncRNA）近来受到越来越多的关注，因为它作为一种竞争性内源性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，为了探究CCA的致癌机制并提高治疗效果，本研究对包括lncRNA、miRNA和mRNA数据在内的表达谱进行了全面整合与分析。对来自癌症基因组图谱（TCGA）数据库的36个CCA样本和9个正常样本的RNA测序和miRNA谱数据进行了全面比较。然后，利用四个公共数据库建立了失调的lncRNA相关ceRNA网络。总之，1410个lncRNA、64个miRNA和3494个mRNA表现为在CCA中异常表达的基因。接着，构建了与lncRNA相关的失调ceRNA网络。该网络包含116个lncRNA、13个miRNA和60个CCA特异性的mRNA。生存分析表明，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在基因表达综合数据库（GEO）中验证其表达水平。结果表明，这些基因在TCGA和GEO数据库之间的表达高度一致。本研究的结果有助于更好地理解参与CCA生物学过程的ceRNA网络，并为改善CCA的诊断和预后奠定坚实基础。
