miR-1827抑制甲状腺乳头状癌细胞增殖、侵袭转移及对c-Myc基因表达的影响  

MiR-1827 inhibits the proliferation,invasion and metastasis of thyroid papillary cancer cells and influences the expression of c-Myc gene through Akt-mTOR pathway

作　　者：胡中保 孟平[1] 陈敬生[1] 陈永忠[1] 李明[1] Zhongbao Hu;Ping Meng;Jingsheng Chen;Yongzhong Chen;Ming Li(Oncology Department,E’zhou Central Hospital,E’zhou 436000,China)

机构地区：[1]湖北鄂州市中心医院肿瘤科,鄂州436000

出　　处：《广西医科大学学报》2020年第9期1581-1589,共9页Journal of Guangxi Medical University

基　　金：湖北省卫生健康委员会基金资助项目(No.WJ2019H121)。

摘　　要：目的:探讨微小RNA 1827(miR-1827)对甲状腺乳头状癌细胞增殖、侵袭转移及对c-Myc基因表达的影响。方法:采用实时荧光定量聚合酶链反应(qPCR)检测miR-1827在TPC-1和Nthy-ori 3-1细胞中的表达,分别用CCK-8、细胞侵袭和蛋白质印迹法(Western blot)检测过表达及干扰miR-1827对TPC-1细胞增殖、侵袭和上皮间质转化(EMT)的影响。采用TargetScan和双荧光素酶报告基因实验分析miR-1827与c-Myc之间的作用靶点,通过qPCR和Western blot检测miR-1827和c-Myc之间的调控关系。通过Western blot分析miR-1827对TPC-1细胞中Akt-mTOR通路的影响。雷帕霉素抑制Akt-mTOR通路后,检测miR-1827对甲状腺乳头状癌细胞增殖、侵袭转移以及对c-Myc基因表达的影响。结果:TPC-1细胞中miR-1827表达水平明显低于Nthy-ori 3-1细胞(P<0.01),过表达miR-1827能够抑制TPC-1细胞的增殖和侵袭(P<0.05),E-cadherin蛋白表达量明显上升(P<0.01),N-cadherin蛋白表达量明显下降(P<0.01)。下调miR-1827能够促进TPC-1细胞的增殖、侵袭和EMT(P<0.05)。c-Myc是miR-1827的直接作用靶点,过表达miR-1827抑制c-Myc表达(P<0.01),敲低miR-1827促进c-Myc表达(P<0.01)。miR-1827激活了TPC-1细胞中Akt-mTOR信号通路,雷帕霉素作用于细胞后,明显降低了miR-1827对TPC-1细胞增殖、侵袭和EMT以及c-Myc表达的抑制作用(P<0.05)。结论:miR-1827通过Akt-mTOR途径抑制了甲状腺乳头状癌细胞的增殖、侵袭转移以及c-Myc的表达。Objective:To investigate the effects of RNA-1827(miR-1827)on the proliferation,invasion and metastasis of thyroid papillary cancer cells and on the expression of c-Myc gene.Methods:The expressions of miR-1827 in TPC-1 and Nthy-ori 3-1cells were detected by RT-qPCR.The effects of overexpression and interference with miR-1827 on TPC-1 cells proliferation,invasion and EMT were detected by CCK-8,Transwell and Western blot respectively.TargetScan and dual luciferase reporter gene experiments were used to analyze the target points between miR-1827 and c-Myc.The regulatory relationship between miR-1827 and c-Myc was detected by RTqPCR and Western blot.The effect of miR-1827 on the AktmTOR pathway in TPC-1 cells was analyzed by Western blot.After rapamycin inhibited Akt-mTOR pathway,the effects of miR-1827 on proliferation,invasion and metastasis of thyroid papillary cancer cells and c-Myc gene expression were detected.Results:The expression of miR-1827 in TPC-1 cells was significantly lower than that in Nthy-ori 3-1 cells(P<0.01).Overexpression of miR-1827 inhibited the proliferation and invasion of TPC-1 cells(P<0.05).The expression of E-cadherin protein was significantly increased(P<0.01),while that of Ncadherin protein was significantly decreased(P<0.01).Downregulation of miR-1827 could promote the proliferation,invasion and EMT of TPC-1 cells(P<0.05).c-Mycwas a direct target of miR-1827.Overexpression of miR-1827 inhibited the expression of c-Myc(P<0.01),and down-regulation of miR-1827 promoted the expression of c-Myc(P<0.01).miR-1827 activated the Akt-mTOR signaling pathway in TPC-1 cells and rapamycin significantly reduced the inhibition of miR-1827 on the proliferation,invasion,EMT and the expression of c-Myc in TPC-1 cells(P<0.05).Conclusion:miR-1827 inhibits the proliferation,invasion and metastasis of thyroid papillary cancer cells and the expression of c-Myc through the Akt-mTOR pathway.

关 键 词：微小RNA 1827 Akt-mTOR信号通路 C-MYC 甲状腺乳头状癌 增殖 侵袭 

分 类 号：R736.1[医药卫生—肿瘤]