EGFR-AKT信号通路下调肺癌细胞miR-145的表达  

EGFR-AKT signaling pathway down- regulates miRNA-145 in lung cancer cells

作　　者：郭跃辉[1] 姜斌[1] 时婧[1] 王炯轶[1] 袁海花[1] 

机构地区：[1]上海交通大学医学院附属第三人民医院肿瘤科,上海201900

出　　处：《现代肿瘤医学》2013年第12期2652-2655,共4页Journal of Modern Oncology

基　　金：上海交通大学医学院科技基金项目(编号:11XJ-22014);上海交通大学医学院附属第三人民医院基金项目(编号:syz2011-05)

摘　　要：目的:研究人肺癌细胞中EGFR的活化对miR-145表达的影响及其可能的分子机制。方法:选择人肺癌细胞株H1975,采用实时荧光定量PCR和Western blot法检测细胞中miR-145的表达水平和EGFR的活化水平。分别以EGF、特异性EGFR酪氨酸激酶抑制剂AG1478、AKT小分子抑制剂LY294002和AKT siRNA处理H1975细胞,观察细胞miR-145的表达情况。结果:肺癌细胞中活化的EGFR下调miR-145的表达,EGF可下调肺癌细胞内miR-145表达,AG1478可逆转EGFR活化所诱导miR-145的下调。EGFR活化后激活下游信号蛋白分子AKT,LY294002抑制AKT活化而恢复EGFR活化所诱导的miR-145下调。AKT siRNA下调AKT蛋白表达,降低pAKT的表达,进而上调miR-145表达。结论:在肺癌细胞中,EGFR可通过AKT信号分子下调miR-145的表达。Objective ： To investigate the effect of EGFR activation on miR - 145 levels in human lung cancer cells and explore the molecular mechanism. Methods：Human lung cancer cell lines （H1975） was chosen, the levels of miR - 145 and p - EGFR were determined by quantitative real - time PCR（ qRT - PCR） and Western blotting respective- ly. The miR - 145 levels were determined by qRT - PCR after activating EGFR with EGF or blocking EGFR signaling pathway with AG1478. In addition,AKT inhibitor LY294002 or AKT siRNA was used to inhibit AKT activation and then the expression was detected. Results：In lung cancer cells, EGFR activation down -regulated the levels of miR - 145. EGF lower the levels of miR - 145, however, miR - 145 was up - regulated after inactivating EGFR with AG1478. The AKT signal pathway was activated by p - EGFR. LY294002 restored the miR - 145 down - regulation induced by EGFR - activation in lung cancer cells. Furthermore, the express of total AKT protein was knocked - down by AKT siRNA, resulting in the elevated levels of miR - 145. Conclusion： The activation of EGFR down - regnlates miRNA - 145 expression through AKT in lung cancer cells.

关 键 词：肺肿瘤 微小RNA-45 表皮生长因子受体 蛋白激酶B 信号转导 

分 类 号：R730.43[医药卫生—肿瘤] R734.2[医药卫生—临床医学]