miR-182激活PI3K/AKT信号通路促进肝癌HepG2细胞增殖、侵袭和迁移的机制研究  

Mechanism research of miR-182 promoting proliferation,invasion and migration of HepG2 cells by activating PI3K/AKT signaling pathway

作　　者：王开琼[1] 邢贻雷[1] 余智威 吴奕强[1] 乔欣 郑进方[1] Wang Kaiqiong;Xing Yilei;Yu Zhiwei;Wu Yiqiang;Qiao Xin;Zheng Jinfang(Department of Biliary and Pancreatic Surgery,Hainan General Hospital,Hainan Haikou 570311,China)

机构地区：[1]海南省人民医院肝胆胰外科,海南海口570311

出　　处：《现代肿瘤医学》2020年第11期1855-1859,共5页Journal of Modern Oncology

摘　　要：目的:探讨miR-182通过PI3K/AKT信号通路对肝癌HepG2细胞增殖、侵袭和迁移的影响及其机制。方法:将体外培养的HepG2细胞分为对照组(未转染)、阴性组(转染阴性对照)、模拟物组(转染miR-182模拟物)和模拟物+抑制剂组(转染miR-182模拟物后,加入PI3K/AKT信号通路抑制剂LY294002),采用RT-PCR检测各组细胞中miR-182的表达水平,Western blot检测各组细胞中PI3K/AKT信号通路相关蛋白PI3K、p-PI3K、AKT、p-AKT和MMP-9、c-Myc、VEGF蛋白的表达,采用MTT法、克隆形成实验和Transwell小室分别检测各组细胞的增殖、侵袭和迁移能力。结果:与对照组相比,模拟物组细胞的存活率、克隆形成率和侵袭细胞数、迁移细胞数均明显升高,细胞中p-PI3K、p-AKT和MMP-9、c-Myc、VEGF蛋白的表达水平也均明显上升(P<0.05);而阴性组和对照组细胞相比无显著性差异(P>0.05)。与模拟物组相比,模拟物+抑制剂组细胞的存活率、克隆形成率和侵袭细胞数、迁移细胞数明显降低,细胞中p-PI3K、p-AKT和MMP-9、c-Myc、VEGF蛋白的表达水平也均明显下降(P<0.05)。结论:miR-182可通过激活PI3K/AKT信号通路上调MMP-9、c-Myc、VEGF蛋白的表达促进肝癌细胞的增殖、侵袭和迁移。Objective:To investigate the effect of miR-182 on the proliferation,invasion and migration of hepatocellular carcinoma HepG2 cells through PI3 K/AKT signaling pathway and its mechanism.Methods:HepG2 cells cultured in vitro were divided into control group(untransfected),negative group(transfected negative control),mimic group(transfected miR-182 mimic)and mimic+inhibitor group(After transfection of miR-182 mimic,PI3 K/AKT signal pathway inhibitor LY294002 was added).The expression of miR-182 was detected by RT-PCR.The expression of PI3 K/AKT signaling pathway related proteins PI3 K,p-PI3 K,AKT,p-AKT,MMP-9,c-Myc and VEGF was detected by Western blot.The proliferation,invasion and migration ability of cells in each group were detected by MTT method,clone formation test and Transwell chamber,respectively.Results:Compared with the control group,the survival rate,colony formation rate,number of invasive cells and migrating cells in the mimic group were significantly increased,and the expression levels of p-PI3 K,p-AKT,MMP-9,c-Myc and VEGF proteins in the cells were also significantly increased(P<0.05),while there was no significant difference between the negative group and the control group(P>0.05).Compared with the mimic group,the survival rate,colony formation rate,number of invasive cells and migrating cells in the mimic+inhibitor group were significantly decreased,and the expression levels of p-PI3 K,p-AKT,MMP-9,c-Myc and VEGF proteins in the cells were also significantly decreased(P<0.05).Conclusion:miR-182 can promote the proliferation,invasion and migration of hepatocellular carcinoma cells by activating PI3 K/AKT signaling pathway and up-regulating the expression of MMP-9,c-Myc and VEGF proteins.

关 键 词：肝癌 miR-182 细胞增殖 侵袭 迁移 PI3K/AKT信号通路 

分 类 号：R735.7[医药卫生—肿瘤]