Downregulation of miR-24 Enhances Cisplatin Sensitivity in Breast Cancer Cells

Abstract

GSK-3β is a tumor suppressor gene in multiple cancers by phosphorylated degrading β-catenin. Several studies showed association of miR-24 with breast cancer. Bioinformatics analysis showed a relationship of miR-24 with GSK-3β. Our study assessed miR-24’s role in GSK-3β/β-catenin siganling and breast cancer cell cisplatin resistance. MiR-24, GSK-3β, β-catenin, and Bcl-2 expressions in MDA-MB-231 and MDA-MB-231/DDP cells were detected along cell proliferation and apoptosis. DDP resistance cells were assigned into miR-NC, miR-24 inhibitor, pIRES-blank, pIRES-GSK-3β, and miR-24 inhibitor+pIRES-GSK-3β groups and cell proliferation was determined. MiR-24 inhibited GSK-3β level. GSK-3β and cell apoptosis significantly downregulated, while miR-24, β-catenin, Bcl-2, and cell proliferation significantly elevated in DDP resistance cells. MiR-24 inhibitor and/or pIRES-GSK-3β significantly increased GSK-3β level, declined β-catenin and Bcl-2 expressions, attenuated cell proliferation, enhanced cell apoptosis, and weakened cisplatin resistance. MiR-24 upregulation was related to breast cancer cell cisplatin resistance. Inhibition of miR-24 upregulated GSK-3β, restrained Wnt/β-catenin signaling and cisplatin resistance in breast cancer cells.