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Long Non-coding RNA PVT1 Promotes Cell Proliferation and Migration by Silencing ANGPTL4 Expression in Cholangiocarcinoma
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2018-10-10 , DOI: 10.1016/j.omtn.2018.10.001
Yang Yu , Mingjiong Zhang , Jie Liu , Boming Xu , Jian Yang , Ni Wang , Shuai Yan , Fei Wang , Xuezhi He , Guozhong Ji , Quanpeng Li , Lin Miao

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention.



中文翻译:

长非编码RNA PVT1通过沉默胆管癌中的ANGPTL4表达来促进细胞增殖和迁移。

胆管癌(CCA)是最常见的胆道恶性肿瘤,生存率低且治疗选择有限。长的非编码RNA(lncRNA)最近已被证实在许多人类癌症中具有重要的调节功能。在这项研究中发现,在CCA中表达明显升高的lncRNA PVT1可能是CCA的分子标记。实验表明,PVT1基因敲除大大抑制了细胞的迁移和体外体内的增殖。根据RNA测序(RNA-seq)分析,PVT1击倒极大地影响了与细胞血管生成,细胞增殖和凋亡过程相关的靶基因。RNA免疫沉淀(RIP)分析表明,通过与表观遗传修饰复合物(PRC2)结合,PVT1可以调节ANGPTL4(血管生成素样4)启动子的组蛋白甲基化,从而促进细胞生长,迁移和凋亡进程。数据证实了PVT1在CCA肿瘤发生中的重要功能,并表明PVT1可能是CCA干预的目标。

更新日期:2018-10-10
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