miR-3691-5p靶向抑制TET1表达促进肝癌细胞迁移与侵袭  

miR-3691-5p promotes hepatocellular carcinoma cell migration and invasion by targeting TET1

作　　者：丁琭 王亮[2] 石磊[2] TETDING Lu;WANG Liang;SHI Lei(Department of Anesthesiology,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Department of Hepatobiliary Surgery,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院麻醉科,陕西西安710061 [2]西安交通大学第一附属医院肝胆外科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2020年第1期84-89,96,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省重点研发计划项目(No.2015SF039)~~

摘　　要：目的探讨肝细胞癌(hepatocellular carcinoma,HCC)中miR-3691-5p的表达、临床意义及作用机制。方法实时定量PCR(qPCR)检测miR-3691-5p在HCC组织与癌旁组织、正常肝细胞(L02)与HCC细胞系中的表达;TCGA数据库分析正常肝组织及肝癌组织中miR-3691-5p的表达差异,分析miR-3691-5p的表达与HCC患者临床病理特征及预后的关系;在MHCC97-H细胞中敲减miR-3691-5p,Transwell实验评价细胞侵袭及迁移能力;TargetScan数据库预测下游靶基因,并通过双荧光素酶报告基因实验加以验证。结果与癌旁组织和正常肝细胞相比,miR-3691-5p在HCC组织及细胞系中均呈现高表达(P<0.05),并与门静脉侵犯(P=0.006)、TNM分期(P=0.008)及Edmondson分级(P=0.001)有关;基于TCGA数据库数据的生存分析显示,miR-3691-5p高表达与不良预后相关(P=0.016);在MHCC97-H细胞中敲减miR-3691-5p抑制细胞的侵袭及迁移;通过生物信息学预测并通过双荧光素酶报告基因实验证实,TET1(Ten-Eleven Translocation 1)是miR-3691-5p的直接靶基因,回复实验证实TET1介导了miR-3691-5p对肝癌细胞侵袭及迁移能力的促进作用。结论miR-3691-5p在HCC中通过靶向抑制抑癌基因TET1促进肝癌细胞侵袭及迁移。Objective To investigate the expression level,clinical significance and mechanisms of miR-3691-5p in hepatocellular carcinoma(HCC).Methods Real-time quantitative PCR(qPCR)was performed to detect miR-3691-5p expression in HCC tissues and the adjacent non-tumor tissues as well as in HCC cell lines and normal hepatic cells.The abundance of miR-3691-5p between normal liver tissues and HCC tissues was analyzed by TCGA database.The relations of miR-3691-5p expression with the clinicopathologic features and prognosis of HCC patients were analyzed.After the MHCC97-H was transfected with miR-3691-5p inhibitors or negative control sequence,the abilities of cell migration and invasion were measured by Transwell assay;the potential downstream of miR-3691-5p was predicted by TargetScan and validated by luciferase reporter assay.Results Compared with tumor adjacent tissues or normal hepatic cells,miR-3691-5p was increased in HCC tissues and cell lines(all P<0.05);the miR-3691-5p expression was significantly related to the portal vein infiltration(P=0.006),advanced TNM stage(P=0.008)and advanced Edmondson degree(P=0.001).The result of overall survival investigated by TCGA database showed that the survival rate in patients with high miR-3691-5p expression was significantly lower than that in those with low miR-3691-5p expression(P=0.016).Knockdown of miR-3691-5p significantly inhibited MHCC97-H cell migration and invasion compared with negative controls.TET1(Ten-Eleven Translocation 1),as the potential downstream of miR-3691-5p,was validated by luciferase reporter assay.Rescue assay showed that TET1 mediated the effects of miR-3691-5p on migration and invasion of HCC cells.Conclusion miR-3691-5p is upregulated in HCC,which promotes HCC cell migration and invasion by targeting TET1.

关 键 词：miR-3691-5p 肝细胞癌 TET1 迁移 侵袭 

分 类 号：R735.7[医药卫生—肿瘤]