MiR-486-5p enhances cisplatin sensitivity of human muscle-invasive bladder cancer cells by induction of apoptosis and down-regulation of metastatic genes

ObjectivesCisplatin is one of the common chemotherapy drugs for bladder cancer, and resistance to this drug is one of the major obstacles to effective chemotherapy. MicroRNAs (miRNAs) are a category of small noncoding RNAs that can regulate the expression of numerous genes. Recent studies showed that miRNAs can act as a powerful regulator of chemo-sensitivity in cancer cells. Hence, this study aimed to investigate the effects of miRNA-486-5p on cisplatin-sensitivity of different bladder cancer cells.Material and MethodsThe 5637 and EJ138 cancer cells were treated with miRNA-486-5p and cisplatin, individually or in combination.ResultsAfterward, the cytotoxicity effects of these treatments were determined by MTT assay and the increased cisplatin-sensitivity observed in both cell lines, especially, 5637 cells. Moreover, subG1 phase cell cycle arrest, changes in the expression of caspase-9, caspase-3, P53, SIRT1, OLFM4, SMAD2, and Bcl-2 genes and nuclear fragmentation also revealed the induction of apoptosis in all treatments, which increased in combination groups. Also, the combination of miRNA-486-5p with cisplatin significantly down-regulated the expression of migration associated genes including ROCK, CD44, and MMP-9 as compared with cisplatin alone.ConclusionAltogether, these results indicated that the miRNA-486-5p could induce apoptosis and inhibit cell migration ability of the cells. It seems that pre-electroporation of cells with miRNA-486-5p has useful results in the enhancement of cisplatin sensitivity of 5637 and EJ138 cancer cells and this combination may be a promising treatment strategy for bladder cancer therapy.