miR-451a通过靶向调节MEF2D抑制膀胱癌细胞的增殖、迁移和侵袭

miR-451a suppresses bladder cancer cell proliferation, migration and invasion by targeting MEF2D

目的研究miR-451a在膀胱癌中的表达及对膀胱癌发生发展的影响。方法通过实时定量PCR(real-time PCR)检测miR-451a在膀胱癌细胞系及组织标本中的表达。采用real-time PCR和Western blot检测MEF2D在膀胱癌组织及转染miR-451a mimics和inhibitor的T24细胞中的表达。双荧光素酶基因报告实验分析MEF2D是否为miR-451a直接的靶基因。通过MTT,Transwell迁移和侵袭实验检测T24细胞在转入miR-451a mimics和inhibitor后细胞增殖、迁移和侵袭能力的变化。结果 miR-451a在膀胱癌细胞及组织中的表达水平下调。miR-451a抑制了T24细胞的增殖、迁移和侵袭。双荧光素酶基因报告证实MEF2D为miR-451a的直接靶基因。miR-451a能够降低T24细胞MEF2DmRNA和蛋白表达水平。结论 miR-451a在膀胱癌中表达下调,通过靶向调节MDF2D起到了抑癌的作用,可能成为膀胱癌诊疗的潜在靶点。

Objective To explore the expression of miR-451 a in bladder cancer(BCa) and elucidate the effect of miR-451 a on the development and progression of BCa. Methods The expression of miR-451 a in BCa cell lines and tissue specimens was detected by using real-time PCR. MEF2 D expression in tissue specimens and BCa cells transfected with miR-451 a mimics and inhibitors was detected by real-time PCR and Western blot. Dual-luciferase reporter assay was performed to confirm that MEF2 D gene is a direct target of miR-451 a, and in vitro cell function testing, MTT, Transwell assay were performed to examine T24 cells proliferation, migration and invasion ability after transfection with miR-451 a mimics and inhibitors. Results miR-451 a was found to be downregulated in BCa cells and tissues, miR-451 a inhibited proliferation, migration and invasion of T24 cells. Dual luciferase reporter assay confirmed that MEF2 D gene was a direct target of miR-451 a and miR-451 a was able to reduce MEF2 D mRNA and protein expression. Conclusion miR-451 a is significantly downregulated in BCa and plays a tumor suppressor role via targeting MEF2 D, and is a potential therapeutic target in the treatment of Bca.