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, β-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 β-catenin mRNA. Reintroduction of β-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 β-catenin.
Conclusion: miR-370-3p suppresses glioma cell growth by directly targeting β-catenin, suggesting that the miR-370-3p/β-catenin axis may be a target for glioma therapy.
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http://dx.doi.org/10.1016/j.brainres.2016.04.066 | DOI Listing |
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