MiR-30a increases cisplatin sensitivity of gastric cancer cells through suppressing epithelial-to-mesenchymal transition (EMT).

Objective MiR-30a can target multiple proteins involved in epithelial-to-mesenchymal transition (EMT). In this study, we investigated the association between miR-30a and cisplatin (DDP) sensitivity in gastric cancer. In addition, the regulation of miR-30a in EMT in SGC-7901 cells and SGC-7901/DDP cells and their involvement in cisplatin sensitivity were further investigated. Patients and methods 20 advanced gastric cancer patients who received platinum-based chemotherapy were recruited. Chemosensitivity was assessed after completion of the therapy. MiR-30a expression was quantified and compared between chemosensitive and chemoresistant groups. SGC-7901 cells and SGC-7901/DDP cells were further used for the in-vitro gain-and-loss study to investigate the effect of miR-30a on EMT and cisplatin sensitivity. Results Chemosensitive patients had significantly higher miR-30a expression than the chemoresistant counterparts. SGC-7901 cells had significantly higher miR-30a expression than SGC-7901/DDP cells. Knockdown of endogenous miR-30a promoted the elongated fibroblast-like morphologic alteration of SGC-7901 cells and also enhanced Snail and Vimentin expression. MiR-30a overexpression induced morphological changes from an extended, fibroblast-like morphology to more epithelial-like morphology in SGC-7901/DDP cells and decreased Snail and Vimentin level. The cancer cells with miR-30a overexpression had significantly higher DDP sensitivity, while the cells with miR-30a knockdown had decreased sensitivity. Conclusions EMT is associated with cisplatin resistance in gastric cancer. MiR-30a is an important miRNA modulating EMT and cisplatin sensitivity of SGC-7901 and SGC-7901/DDP cells.