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.
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