MicroRNA-370-3p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting β-catenin

Objective: The aim of this study was to explore the expression and biological role of miR-370-3p in human gliomas. Methods: Clinical specimens from the brains of 20 glioma patients and 10 healthy controls were obtained to quantify the expression level of miR-370-3p using quantitative real-time PCR. Oligonucleotide mimics of miR-370-3p were transfected into U251 and U87-MG cells for a gain of function assay. The CCK-8 assay, colony formation assay, EdU assay and flow cytometry were used to evaluate the roles of miR-370-3p in cell proliferation and the cell cycle regulation. Western blot and luciferase activity assays were used to investigate the reciprocal relationship between miR-370-3p and its predicted target, beta-catenin. Results: miR-370-3p expression was frequently found to be decreased in glioma tissues, and its expression level was negatively correlated with the malignant degree of the glioma. Overexpression of miR-370-3p showed a significant inhibitory effect on cell proliferation and accompanied cell cycle G0/G1 arrest in U251 and U87-MG cells. Furthermore, miR-370-3p inhibited the expression of the canonical Wnt pathway downstream targets cyclin D1 and c-myc via direct binding interaction with the 3'-untranslated region of beta-catenin mRNA. Reintroduction of beta-catenin could partially reverse the anti-proliferation effect of miR-370-3p. Finally, in 20 glioma tissues the expression of miR-370-3p was negatively correlated with both protein and mRNA levels of beta-catenin. Conclusion: miR-370-3p suppresses glioma cell growth by directly targeting beta-catenin, suggesting that the miR-370-3p/beta-catenin axis may be a target for glioma therapy. (C) 2016 Elsevier B.V. All rights reserved.