MiR-155 affects renal carcinoma cell proliferation, invasion and apoptosis through regulating GSK-3β/β-catenin signaling pathway

Abstract

Objective: Glycogen Synthase Kinase-3β (GSK-3β) negatively regulates Wnt/β-catenin signaling pathway through degrading β-catenin protein. It plays an inhibitory role in various tumors, while the influence in the pathogenesis of renal carcinoma has not been elucidated. MicroRNA-155 (MiR-155) was found to be upregulated in renal carcinoma tissue. Bioinformatics analysis revealed the complementary binding site between miR-155 and 3'-UTR of GSK-3β. This study investigated the influence of miR-155 in regulating GSK-3β expression, Wnt/β-catenin signaling pathway activity, and renal carcinoma cell proliferation, invasion, and apoptosis.

Patients and methods: The targeted regulatory relationship between miR-155 and GSK-3β were tested by dual luciferase assay. Renal carcinoma tissue and benign renal tissue were collected to detect miR-155 and GSK-3β expressions. MiR-155, GSK-3β, and β-catenin levels were compared between HK-2 and 786-O cells. Renal carcinoma 786-O cells were cultured in vitro and divided into four groups, including miR-NC, anti-miR-155, pIRES2-blank, and pIRES2-GSK-3β groups. Cell apoptosis was evaluated by flow cytometry. Cell invasion was determined by transwell assay. Cell proliferation was assessed by EdU staining.

Results: MiR-155 targeted regulated GSK-3β expression. MiR-155 and β-catenin expressions were significantly increased, while GSK-3β level was significantly declined in renal carcinoma tissue compared with benign renal tissue. MiR-155 and β-catenin expressions were significantly elevated, whereas GSK-3β level was significantly downregulated in 786-O cells compared with HK-2 cells. Anti-miR-155 or pIRES2-GSK-3β transfection significantly up-regulated GSK-3β expression, attenuated β-catenin level, restrained cell proliferation and invasion, and enhanced cell apoptosis.

Conclusions: MiR-155 promoted renal carcinoma pathogenesis. Inhibition of miR-155 increased GSK-3β expression, attenuated Wnt/β-catenin signaling pathway, weakened proliferation and invasion, and facilitated apoptosis in renal carcinoma cells.