miR-190-5p靶向抑制PHLPP1的表达促进肺腺癌A549细胞增殖和转移  

miR-190-5p targeted inhibition of PHLPP1 expression promotes proliferation and metastasis of lung adenocarcinoma A549 cells

作　　者：黄小琴 贾玉芳 莫婷 余华军 张召 廖卫平 张海涛 HUANG Xiaoqin;JIA Yufang;MO Ting;YU Huajun;ZHANG Zhao;LIAO Weiping;ZHANG Haitaoi(The Fourth People's Hospital of Foshan,Foshan 528000,China;Department of Biochemistry,Guangdong Medical University,Zhanjiang 524023,China)

机构地区：[1]佛山市第四人民医院呼吸科,佛山528000 [2]广东医科大学生物化学与分子生物学教研室,湛江524023

出　　处：《生命的化学》2023年第9期1445-1455,共11页Chemistry of Life

基　　金：佛山市第四人民医院“登峰计划”高水平医院建设开放课题(FSSYKF-2020019)。

摘　　要：miR-190-5p是小分子非编码RNA,参与调控肺腺癌细胞的增殖和转移。对miR-190-5p调控肺腺癌细胞的增殖和转移的机制深入研究会帮助了解到肺腺癌的发生机制和探究潜在的药物干预靶点。本文研究了miR-190-5p对肺腺癌A549细胞的增殖和转移的影响,解释了miR-190-5p促进肺腺癌生长的机制;通过感染miR-190-5p的慢病毒表达系统,克隆了稳定过表达miR-190-5p的肺腺癌A549细胞系;通过生物信息学方法和荧光素酶报告实验确认了miR-190-5p的靶基因。结果发现,稳定过度表达的miR-190-5p能促进A549细胞的增殖和转移;确定了miR-190-5p的靶点是PH域富含亮氨酸重复的蛋白磷酸酶1(Leucine-rich repeat-rich protein phosphatase 1 in the PH domain,PHLPP1),miR-190-5p降低PHLPP1蛋白水平;稳定表达的miR-190-5p增加了A549细胞中E盒结合锌指蛋白1(E box-binding zinc finger protein1,TCF8/ZEB1)、锌指转录因子(Zinc finger transcription factor,Snail)、具有凝血酶原基序的解体蛋白和金属蛋白酶1(a disintegrin and metalloproteinase with thrombospondin motifs 1,ADAMTS1)的表达和蛋白激酶B(protein kinase B,AKT)在Ser473的磷酸化,而过表达PHLPP1削弱了miR-190-5p的功能,降低了miR-190-5p促进A549细胞的增殖、迁移和侵袭能力;miR-190-5p通过抑制PHLPP1的表达而增强了A549细胞的增殖和转移。这表明,miR-190-5p可能可以作为肺腺癌治疗的潜在靶点。miR-190-5p is a small molecule non-coding RNA that participates in the regulation of lung adenocarcinoma cell proliferation and metastasis.An intensive study of the mechanisms by which miR-190-5p regulates the proliferation and metastasis of lung adenocarcinoma cells will help to understand the mechanism of lung adenocarcinogenesis and explore potential targets for drug intervention.Consequently,we study the effects of miR-190-5p on the proliferation and metastasis of lung adenocarcinoma A549 cells and explain the mechanism of miR-190-5p promoting the growth of lung adenocarcinoma.A lung adenocarcinoma cell line A549 with stable overexpression of miR-190-5p was cloned through a lentivirus expression system infected with miR-190-5p.The target genes of miR-190-5p were identified by bioinformatics and luciferase reporter assays.Stably overexpressed miR-190-5p promoted the proliferation and metastasis of A549 cells.The target of miR-190-5p was identified as PHLPP1.miR-190-5p decreased PHLPP1(leucine-rich repeat-rich protein phosphatase 1 in the PH domain)protein levels.Stable expression of miR-190-5p increased the expression of TCF8/ZEB1,Snail,ADAMTS1 and the phosphorylation of AKT at Ser 473 in A549 cells.Overexpression of PHLPP1 weakened the function of miR-190-5p and reduced the ability of miR-190-5p to promote the proliferation,migration and invasion of A549 cells.miR-190-5p enhanced the proliferation and metastasis of A549 cells by inhibiting the expression of PHLPP1.miR-190-5p may be a potential target for the treatment of lungadenocarcinoma.

关 键 词：miR-190-5p 肺癌 PH域富含亮氨酸重复的蛋白磷酸酶1 增殖 转移 

分 类 号：R734.2[医药卫生—肿瘤]