下调miR-141-3p对晚期NSCLC细胞侵袭转移和化疗敏感性影响及其机制  

EFFECT OF MIR-141-3P DOWNREGULATION ON THE INVASION, MIGRATION, AND CHEMOSENSITIVITY OF ADVANCED NON-SMALL CELL LUNG CANCER CELLS AND ITS MECHANISM

作　　者：王亚飞[1] 张振军[1] 宋长亮[1] 张磊[2] WANG Yafei;ZHANG Zhenjun;SONG Changliang;ZHANG Lei(Oncology Department,Handan Central Hospital,Handan 056000,China)

机构地区：[1]邯郸市中心医院肿瘤科,河北邯郸056000 [2]冀中能源峰峰集团总医院邯郸分院骨科

出　　处：《青岛大学学报（医学版）》2021年第2期228-233,共6页Journal of Qingdao University(Medical Sciences)

基　　金：河北省医学科学研究课题计划项目(20191834)。

摘　　要：目的研究miR-141-3p介导Yes相关蛋白1(YAP1)基因表达对晚期非小细胞肺癌(NSCLC)细胞侵袭转移和化疗敏感性的影响及其作用机制。方法收集50例晚期NSCLC及癌旁组织标本,采用定量逆转录聚合酶链反应(qRT-PCR)检测组织中miR-141-3p和YAP1表达量。选择NSCLC细胞株,设计miR-141-3p inhibitor和siRNA-YAP1,将细胞分为Blank组、miR-141-3p mimic组、miR-141-3p inhibitor组、YAP1 vector组、siRNA-YAP1组和miR-141-3p mimic+siRNA-YAP1组。取对数生长期的细胞接种于96孔培养板,加10 mg/L顺铂置37℃、体积分数0.05 CO 2条件下培养;观察细胞迁移、侵袭、耐药性的变化,并检测miR-141-3p、YAP1、TGF-β信号通路相关蛋白TGF-β和Smad2表达。结果与癌旁组织相比,晚期NSCLC中miR-141-3p和YAP1呈高表达(t=23.19、17.32,P均<0.05)。过表达miR-141-3p或YAP1能够降低TGF-β和Smad2表达,促进癌细胞侵袭迁移,降低顺铂处理后细胞存活率(Tukey’s检验,P均<0.05);而沉默miR-141-3p或YAP1能够提高TGF-β和Smad2表达,抑制癌细胞转移侵袭,提高顺铂处理后细胞存活率(Tukey’s检验,P均<0.05;F=82.670~181.000,P均<0.05)。结论miR-141-3p下调可能通过抑制YAP1基因表达激活TGF-β信号通路,进而调控晚期NSCLC细胞侵袭转移和化疗敏感性。Objective To investigate the effect of the gene expression of Yes-associated protein 1(YAP1)mediated by miR-141-3p on the invasion,migration,and chemosensitivity of advanced non-small cell lung cancer(NSCLC)cells.Methods Advanced NSCLC and adjacent tissue samples were collected from 50 patients,and quantitative reverse transcription-polymerase chain reaction was used to measure the expression of miR-141-3p and YAP1.NSCLC cell line was selected,and miR-141-3p inhibitor and siRNA-YAP1 were designed.The cells were divided into blank group,miR-141-3p mimic group,miR-141-3p inhibitor group,YAP1 vector group,siRNA-YAP1 group,and miR-141-3p mimic+siRNA-YAP1 group.The cells in the logarithmic growth phase were inoculated on a 96-well plate and cultured with 10 mg/L cisplatin at 37℃and a volume fraction of CO 2 of 0.05;the changes in cell migration,invasion,and drug resistance were observed,and the expression of miR-141-3p,YAP1,and proteins related to the TGF-βsignaling pathway(TGF-βand Smad2)was measured.Results Compared with the adjacent tissue,the advanced NSCLC tissue showed high expression of miR-141-3p and YAP1(t=23.19,17.32;P<0.05).Overexpression of miR-141-3p or YAP1 reduced the expression of TGF-βand Smad2,promoted the invasion and migration of cancer cells,and reduced cell viability after cisplatin treatment(Tukey’s test,P<0.05),while silencing of miR-141-3p or YAP1 increased the expression of TGF-βand Smad2,inhibited the migration and invasion of cancer cells,and increased cell viability after cisplatin treatment(Tukey’s test,P<0.05;F=82.670-181.000,P<0.05).Conclusion Downregulation of miR-141-3p may regulate the invasion,migration,and chemosensitivity of advanced NSCLC cells by inhibiting the expression of the YAP1 gene and activating the TGF-βsignaling pathway.

关 键 词：癌 非小细胞肺 微RNAs RNA干扰 TGF-Β信号通路 肿瘤侵润 肿瘤转移 辐射耐受性 抗药性 肿瘤 

分 类 号：R730.26[医药卫生—肿瘤] R342.2[医药卫生—临床医学]