miR-148a-3p靶向调控FLOT2促进肝癌细胞迁移、侵袭及增殖  

miR-148a-3p targets FLOT2 to promote maligration,invasion and proliferation in hepatocellular carcinoma

作　　者：王芊文 李文华 逯君霞 赵彬 耿玉庆 王小芳 吴向未[1,2,3] 陈雪玲 WANG Qianwen;LI Wenhua;LU Junxia;ZHAO Bin;GENG Yuqing;WANG Xiaofang;WU Xiangwei;CHEN Xueling(Key Laboratory for Prevention and Treatment of Central Asian High Disease,National Health Commission,Xinjiang Shihezi 832000,China;Medical College of Shihezi University,Xinjiang Shihezi 832000,China;Department of Hepatobiliary Surgery,the First Affiliated Hospital of Shihezi University School of Medicine,Xinjiang Shihezi 832000,China)

机构地区：[1]国家卫生健康委中亚高发病防治重点实验室,新疆石河子832000 [2]石河子大学医学院,新疆石河子832000 [3]石河子大学医学院第一附属医院肝胆外科,新疆石河子832000

出　　处：《现代肿瘤医学》2023年第21期3921-3927,共7页Journal of Modern Oncology

基　　金：中国医学科学院中央级公益性科研院所基本科研业务费专项资金资助(编号:2020-PT330-003);国家自然地区科学基金项目(编号:82060297);兵团指导性科技计划项目(编号:2022ZD041);兵团财政科技计划项目区域创新引导计划(编号:2021BB006);石河子大学自主支持科研项目(编号:ZZZC202026A)。

摘　　要：目的:探究脂筏特征蛋白2(Flotillin2,FLOT2)对肝癌细胞迁移、侵袭和增殖能力的影响及相关机制。方法:通过ENCORI数据库和细胞功能学实验证实FLOT2在肝癌中的表达情况以及对肝癌细胞生物学行为的影响;TargetScan中检索可能调控FLOT2的miRNA,CancerMIRNome分析miR-148a-3p在肝癌中的表达和对肝癌患者预后的影响,qRT-PCR和Western Blot检测过表达miR-148a-3p后肝癌细胞中FLOT2的表达水平,双荧光素酶实验验证miR-148a-3p与FLOT2的靶向调控关系;将细胞分为pcDNA组、pcDNA-FLOT2组以及pcDNA-FLOT2+miR-148a-3p mimics组,Transwell实验以及EdU实验检测三组细胞迁移、侵袭和增殖能力。结果:FLOT2在肝癌中高表达,高表达FLOT2的肝癌患者预后更差,过表达FLOT2增强肝癌细胞的迁移、侵袭和增殖能力;miR-148a-3p在肝癌组织中低表达,与肝癌患者预后相关,和FLOT2呈负相关;过表达miR-148a-3p降低FLOT2的mRNA和蛋白水平,双荧光素酶实验表明miR-148a-3p靶向调控FLOT2基因;过表达miR-148a-3p抑制FLOT2促进肝癌细胞迁移、侵袭和增殖的能力。结论:miR-148a-3p靶向调控FLOT2基因促进肝癌细胞迁移、侵袭及增殖。Objective:To investigats the effect of lipid raft signature protein 2(Flotillin2,FLOT2)on migration,invasion and proliferation of hepatocellular carcinoma and related mechanisms.Methods:The expression of FLOT2 in hepatocellular carcinoma and its effect on the biological behavior of hepatocellular carcinoma cells were confirmed by the ENCORI database and cell functional assays.miRNAs that may regulate FLOT2 were retrieved in TargetScan,and miR-148a-3p expression in hepatocellular carcinoma and its effect on the prognosis of hepatocellular carcinoma patients were analyzed in CancerMIRNome.qRT-PCR and Western Blot were performed to detect the expression level of FLOT2 in hepatocellular carcinoma after overexpression of miR-148a-3p.Dual luciferase assay was performed to verify the targeting and regulation of miR-148a-3p and FLOT2.The cells were divided into pcDNA,pcDNA-FLOT2 and pcDNA-FLOT2+miR-148a-3p mimics groups,and the migration,invasion and proliferation abilities of the three groups were measured by Transwell assay and EdU assay.Results:FLOT2 was highly expressed in hepatocellular carcinoma,and patients with high FLOT2 expression had a worse prognosis.Overexpression of FLOT2 enhanced the migration,invasion and proliferation of hepatocellular carcinoma cells.miR-148a-3p was lowly expressed in hepatocellular carcinoma tissues,correlated with the prognosis of hepatocellular carcinoma patients,and was negatively correlated with FLOT2.Dual luciferase assay verified that the targeted regulation of FLOT2 gene by miR-148a-3p.Overexpression of miR-148a-3p decreases the mRNA and protein levels of FLOT2.Overexpression of miR-148a-3p inhibited the ability of FLOT2 to promote the migration,invasion and proliferation of hepatocellular carcinoma cells. Conclusion: miR-148a-3p targeted regulation of FLOT2 gene affect the migration,invasion and proliferation of hepatoma cells.

关 键 词：肝癌 miR-148a-3p FLOT2 迁移 增殖 

分 类 号：R735.7[医药卫生—肿瘤]