过表达miR-145-5p通过下调IGF1R抑制食管鳞状细胞TE-10细胞的恶性生物学行为  

Over-expression of miR-145-5p inhibits malignant biological behaviors of esophageal squamous cells carcinoma via down-regulating IGF1R

作　　者：邴钟兴[1] 曹磊[1] 曹智理[1] 梁乃新[1] BING Zhongxing;CAO Lei;CAO Zhili;LIANG Naixin(Department of Thoracic Surgery,Peking Union Medical College Hospital,Beijing 100005,China)

机构地区：[1]北京协和医院胸外科,北京100005

出　　处：《中国肿瘤生物治疗杂志》2020年第6期634-639,共6页Chinese Journal of Cancer Biotherapy

基　　金：中国医学科学院医学与健康科技创新工程项目(No.2019-I2M-1-001);北京市东城区科学技术委员会优秀人才培养资助项目(No.2018-DCQYXRCXM-012)。

摘　　要：目的:探究miR-145-5p对食管鳞状细胞癌TE-10细胞增殖、侵袭、迁移和上皮间质转化(epithelial-mesenchymal transition,EMT)等恶性生物学行为的分子机制。方法:q PCR法检测miR-145-5p在食管鳞状细胞癌细胞和正常食管上皮细胞中的表达水平。采用双荧光素酶报告基因实验检测miR-145-5p与胰岛素样生长因子1受体(insulin-like growth factor 1 receptor,IGF1R)的靶向调控关系,Western blotting检测IGF1R蛋白和EMT相关蛋白的表达,CCK-8法和Transwell检测miR-145-5p/IGF1R分子轴对TE-10细胞增殖、侵袭、迁移的影响。结果:miR-145-5p在3株食管鳞状细胞癌细胞中低表达且在TE-10细胞中表达最低(P<0.01或P<0.05)。过表达miR-145-5p可显著抑制TE-10细胞的增殖、侵袭、迁移和EMT进程(P<0.01或P<0.05)。双荧光素酶报告基因证实miR-145-5p靶向下调IGF1R表达(P<0.01)。回复实验进一步证实,与单独过表达IGF1R相比,同时过表达miR-145-5p和IGF1R能显著缓解IGF1R对TE-10细胞的增殖、侵袭、迁移和EMT进程的促进作用(P<0.01或P<0.05)。结论:过表达miR-145-5p通过靶向下调IGF1R进而抑制了食管鳞状细胞癌TE-10细胞的增殖、侵袭、迁移和EMT进程。Objective:To explore the mechanism of miR-145-5p on malignant biological behaviors,such as pro-liferation,invasion,migration and epithelial-mesenchymal transition(EMT),of esophageal squamous cell carcinoma(ESCC)TE-10 cells.Methods:The expression of miR-145-5p in ESCC cell lines and normal cells was detected by PCR.Dual luciferase reporter gene assay was used to detect the targeted regulation between miR-145-5p and insulin-like growth factor 1 receptor(IGF1R).The expres-sions of IGF1R protein and EMT related proteins were detected by Western blotting.Transwell assay and CCK-8 assay were carried out to detect the effects of miR-145-5p/IGF1R axis on the proliferation,migration and invasion of TE-10 cells.Results:miR-145-5p was down-regulated in ESCC cell lines with the lowest expression in TE-10 cells(P<0.01 or P<0.05).Over-expression of miR-145-5p significantly inhibited proliferation,invasion,migration and EMT of TE-10 cells(P<0.01 or P<0.05).Dual luciferase reporter gene assay con-firmed that miR-145-5p targetedly down-regulated IGF1R expression(P<0.01).The restora-tion experiments further confirmed that simultaneous over-expression of miR-145-5p and IGF1R significantly attenuated the promotion effect of IGF1R on proliferation,invasion,migration and EMT of TE-10 cells(P<0.01 or P<0.05).Conclusions:Over-expression of miR-145-5p inhibits proliferation,invasion,migration and EMT of ESCC TE-10 cells by down-regulating IGF1R.

关 键 词：食管鳞状细胞癌 TE-10细胞 miR-145-5p 胰岛素样生长因子1受体 增殖 侵袭 迁移 上皮间质转化 

分 类 号：R730.54[医药卫生—肿瘤] R735.1[医药卫生—临床医学]