MiR-9-5p Increases Sensitivity to Cisplatin in Thyroid Cancer Cells by Down-Regulating BRAF Expression

Abstract

Objective: To explore the expression of miR-9-5p and BRAF in cisplatin resistant strain thyroid cancer cells and reversal effect of drug resistance as well as the possible mechanism. Methods: The cisplatin-resistant thyroid cancer cells (FTC-133/DDP and TPC-1/DDP) were respectively divided into 3 groups as NC, DDP and DDP + miRNA groups. Measuring cell proliferation by MTT assay and cell apoptosis by flow cytometry; Evaluating invasion cell number and wound healing rates by transwell and wound healing assay. The relative proteins (BRAF, Mek and Erk1/2) were measured by WB assay. The correlation between miR-9-5p and BRAF by dual-luciferase reporter assay in FTC-133/DDP and TPC-1/DDP cells. Results: In FTC-133/DDP and TPC-1/DDP cells experiment, compared with DDP group, with miR-9-5p supplement, the cell proliferation rats were significantly depressed with cell apoptosis increasing (P < 0.001, respectively); invasion cell number and wound healing rats were significantly down-regulation (P < 0.001, respectively) in DDP + miRNA groups. Meanwhile, the BRAF, Mek and Erk1/2 proteins expressions were significantly depressed in DDP + miRNA groups were significantly suppressed compared with those in DDP groups (P < 0.001, respectively). By dual-luciferase reporter assay, BRAF was the target gene of miR-9-5p in FTC133/DDP and TPC-1/DDP cells. Conclusion: miR-9-5p increases sensitivity to cisplatin in thyroid cancer cells by down-regulating BRAF expression.