RETRACTED: Targeting of GSK-3β by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis (Retracted Article)

OBJECTIVE: Wnt/beta-catenin pathway regulates cell proliferation and apoptosis. GSK-3 beta degrades beta-catenin and negatively regulates Wnt/beta-catenin pathway. A previous study indicated that the GSK-3 beta expression was significantly reduced in gastric cancer, along with the increase of miR-214 expression. Bioinformatics analysis revealed complementary binding sites between miR-214 and 3'-UTR of GSK-3 beta mRNA. This study investigated the regulatory role and related mechanism of miR-214 in the proliferation and apoptosis of gastric cancer cells. PATIENTS AND METHODS: Gastric cancer tissues were collected from patients and the expressions of miR-214, GSK-3 beta and beta-catenin were determined. Dual luciferase reporter gene assay was used to study the regulatory role between miR-214 and GSK-3 beta. Expressions of miR-214, GSK-3 beta, beta-catenin and survivin from GES-1 and MKN-28 cells were detected. Flow cytometry was used to measure cell proliferation and apoptosis. In vitro cultured MKN-28 cells were treated with miR-214 inhibitor and/or pSicoR-GSK-3 beta. Levels of GSK-3 beta, beta-catenin and survivin were detected, cell apoptosis was evaluated by flow cytometry and proliferation was tested by EdU staining. RESULTS: Compared to normal gastric mucosa, the levels of miR-214 and beta-catenin were elevated, and the expression of GSK-3 beta was decreased in gastric cancer tissues. Compared to GES-1 cells, the expressions of miR-214, beta-catenin and survivin in MKN-28 cells were upregulated, along with downregulation of GSK-3 beta expression. The proliferation was enhanced whilst apoptosis was suppressed. After the transfection of miR-214 inhibitor and/or pSicoR-GSK3 beta, GSK-3 beta expression was induced in MKN-28 cells while beta-catenin and survivin expressions were inhibited, along with the increase of cell apoptosis. CONCLUSIONS: MiR-214 decreases GSK-3 beta expression and promotes the pathogenesis of gastric cancer. The inhibition of miR-214 reduces the proliferation of gastric cancer cells via upregulation of GSK-3 beta and suppression of Wnt/beta-catenin signal pathway, which provides fundamental support for the future therapy of gastric cancer.