Yu Yang, Zhang Mingjiong, Liu Jie, Xu Boming, Yang Jian, Wang Ni, Yan Shuai, Wang Fei, He Xuezhi, Ji Guozhong, Li Quanpeng, Miao Lin
Medical Centre for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
Reproduction Centre of Xuzhou Maternity and Child Health Care Hospital, Xuzhou, Jiangsu Province, People's Republic of China.
Mol Ther Nucleic Acids. 2018 Dec 7;13:503-513. doi: 10.1016/j.omtn.2018.10.001. Epub 2018 Oct 10.
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.
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。长链非编码RNA(lncRNAs)最近已被证实在多种人类癌症中具有重要的调节功能。本研究发现,在CCA中表达显著升高的lncRNA PVT1可能是CCA的一个分子标志物。实验表明,PVT1基因敲低在体外和体内均能显著抑制细胞迁移和增殖。根据RNA测序(RNA-seq)分析,PVT1基因敲低显著影响与细胞血管生成、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可以调节血管生成素样4(ANGPTL4)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。这些数据证实了PVT1在CCA肿瘤发生中的重要作用,并表明PVT1可能是CCA干预的一个靶点。