Targeting of GSK-3β by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis

H.-L. Li, S. Liang, J.-H. Cui, G.-Y. Han

The 2nd Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang, China. guangyuhant@126.com

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• Oncology

OBJECTIVE: Wnt/β-catenin pathway regulates cell proliferation and apoptosis. GSK-3β degrades β-catenin and negatively regulates Wnt/β-catenin pathway. A previous study indicated that the GSK-3β 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-3β 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-3β and β-catenin were determined. Dual luciferase reporter gene assay was used to study the regulatory role between miR-214 and GSK-3β. Expressions of miR-214, GSK-3β, β-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-3β. Levels of GSK-3β, β-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 β-catenin were elevated, and the expression of GSK-3β was decreased in gastric cancer tissues. Compared to GES-1 cells, the expressions of miR-214, β-catenin and survivin in MKN-28 cells were upregulated, along with downregulation of GSK-3β expression. The proliferation was enhanced whilst apoptosis was suppressed. After the transfection of miR-214 inhibitor and/or pSicoR-GSK-3β, GSK-3β expression was induced in MKN-28 cells while β-catenin and survivin expressions were inhibited, along with the increase of cell apoptosis.

CONCLUSIONS: MiR-214 decreases GSK-3β expression and promotes the pathogenesis of gastric cancer. The inhibition of miR-214 reduces the proliferation of gastric cancer cells via upregulation of GSK-3β and suppression of Wnt/β-catenin signal pathway, which provides fundamental support for the future therapy of gastric cancer.

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