Long Non-coding RNA PVT1 Promotes Cell Proliferation and Migration by Silencing ANGPTL4 Expression in Cholangiocarcinoma

长链非编码 RNA PVT1 通过沉默胆管癌中的 ANGPTL4 表达促进细胞增殖和迁移

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作者:Yang Yu, Mingjiong Zhang, Jie Liu, Boming Xu, Jian Yang, Ni Wang, Shuai Yan, Fei Wang, Xuezhi He, Guozhong Ji, Quanpeng Li, Lin Miao

Abstract

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.

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