MiR-3622b-5p regulates cisplatin resistance of human gastric cancer cell line by targeting BIRC5

Abstract

Many evidences showed that drug resistance of gastric cancer cells could be regulated by the abnormal expression of microRNAs (miRNAs), a post-transcriptional regulator of gene expression. Thus, we investigated the role of miR-3622b-5p in the development of cisplatin (DDP) resistance in human gastric cancer cell lines. A set of biochemical assays were used to elucidate the mechanism by which miR-3622b-5p regulates drug resistance in cancer cells. The expression of miR-3622b-5p was measured by quantitative real-time PCR and showed that miR-3622b-5p was significantly downregulated in the plasma of patients with acquired drug resistance to platinum-based chemotherapy for gastric cancer. miR-3622b-5p was also found significantly downregulated in DDP-resistant gastric cancer cell line SGC7901/DDP, compared with the parental SGC7901 cells. An in vitro drug sensitivity assay showed that overexpression of miR-3622b-5p sensitized SGC7901/DDP cells to DDP. The luciferase activity of reporters constructed by BIRC5 3′-untranslated regions in SGC7901/DDP cells suggested that BIRC5 was target gene of miR-3622b-5p. Ecpotic miR-3622b-5p expression in SGC7901/DDP cells significantly repressed the expression of the BIRC5 and sensitized the cells to DDP-induced apoptosis. By contrast, treatment with miR-3622b-5p inhibitor increased the protein expression of BIRC5 and led to a lower proportion of apoptotic cells in the SGC7901 cells. In conclusion, our findings suggest that miR-3622b-5p regulates DDP resistance of human gastric cancer cells at least in part by repressing the expression of BIRC5. Altering miR-3622b-5p expression may be a potential therapeutic strategy for the treatment of chemoresistance in gastric cancer in the future.