微小RNA-98-5p靶向调控核糖核苷酸还原酶小亚基M2调控宫颈癌细胞顺铂的耐药性

目的 探讨微小RNA(miR)-98-5p对顺铂(DDP)耐药宫颈癌细胞顺铂敏感性的调控及其机制.方法 用脂质体法将 DDP+miR-NC 组(转染 miR-NC)、DDP+miR-98-5p 组(转染 miR-98-5p mimics)、DDP+si-NC 组(转染si-NC)、DDP+si-核糖核苷酸还原酶小亚基M...

MicroRNA-98-5p targeting ribonucleotide reductase small subunit M2 regulating cisplatin resistance in cervical cancer cells

Objective To investigate the regulation and mechanism of microRNA(miR)-98-5p on cisplatin sensitivity in cisplatin resistant cervical cancer cells. Methods The cisplatin(DDP)+miR-NC group (transfected miR-NC), DDP+miR-98-5p group (transfected miR-98-5p mimics), DDP+si-NC group (transfected si-NC), DDP+si-ribonucleotide reductase subunit M2(RRM2) group (transfected si-RRM2), DDP+miR 98-5p+pcDNA group (co-transfected miR-98-5p mimics and pcDNA), DDP+miR-98-5p+pcDNA-RRM2 group (co-transfected miR-98-5p mimics and pcDNA-RRM2) were transfected into HeLa/DDP cells by liposome method . Real-tim PCR, Western blotting, CCK-8, Transwell chamber and dual luciferase reports gene detection assay were used to detect the expression of miR-98-5p, RRM2, cyclin D1, P21, matrix metalloproteinase(MMP)-2 and MMP-9 in cells, inhibition rate, half inhibitory concentration(IC₅₀), migration and invasion and fluorescence activity. Results Compared with the HeLa group, the expression of miR-98-5p was significantly decreased in HeLa/DDP group, the expression of RRM2 was significantly increased, the IC50 value was significantly increased (P<0.05). Overexpression miR-98-5p or inhibition RRM2 could significantly inhibit the proliferation, migration and invasion of HeLa/DDP cells, down-regulated proteins expression of cyclin D1, MMP-2 and MMP-9, and up-regulated proteins expression of P21; miR-98-5p inhibited the fluorescence activity of wild-type RRM2 cells, and overexpress RRM2 could reverse the inhibitory effect of miR-98-5p on proliferation, migration and invasion of HeLa/DDP cells. Conclusion miR-98-5p can inhibit the proliferation, migration and invasion of cisplatin-resistant cervical cancer cells and enhance the sensitivity to cisplatin. The mechanism is related to the targeting of RRM2, which will provide directions for the treatment of cisplatin-resistant cervical cancer cells.