MiR-148a induces apoptosis by upregulating BIM expression in gastric cancer cells

Background and objective: Gastric cancer is one of the most common malignant diseases worldwide. MicroRNAs (miRNAs) play crucial roles in the regulation of apoptosis. However, the regulation of gastric cancer (GC) apoptosis by miRNAs has not been intensively investigated. To address this issue, the effect of miR-148a on the cell proliferation of gastric cancer SGC7901 cells was characterized in the present study. Methods: We analyzed the expression of miR-148a in gastric cancer SGC7901 cell lines and normal gastric mucosal epithelial GES-1 cell. We examined the effect of miR-148a mimics on the apoptosis and growth of SGC7901 cells in vitro by flow cytometry (FCM) assays, cell cycle analysis, MTT cell viability assay and colony formation assay. Nude mouse xenograft model was used to determine whether miR-148a is involved in tumorigenesis of gastric cancer. The miR-148a target of BIM was identified by western blot analysis and immunohistochemistry. Cell apoptosis was detected by TUNEL assay. Results: MiR-148a was significantly downregulated in SGC7901 cells compared with GES-1 cells. Overexpression miR-148a with miR-148a mimics (miR-148a) initiated G0/G1 cell-cycle arrest, apoptosis and inhibited growth of SGC7901 cells in vitro, and miR-148a could significantly inhibit tumorigenicity of SGC7901 by increasing the apoptosis proportion of cancer cells in vivo. Moreover, BIM was identified as the potential target of miR-148a. Silencing of BIM was able to photocopy the effect of miR-148a overexpression on apoptosis regulation of cancer cells, indicating BIM is potentially involved in miR-148a-induced apoptosis on cancer cells. Conclusions: MiR-148a may function as a novel tumor suppressor gene in gastric cancer by targeting BIM and regulating the apoptosis of cancer cells. MiR-148a could serve as a potential biomarker and therapeutic target against gastric cancer.