Zesheng Peng1, Tingfeng Wu1, Yuntao Li1, Zhou Xu1, Shenqi Zhang1, Baohui Liu1, Qianxue Chen1, Daofeng Tian2. 1. Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China. 2. Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China. Electronic address: tiandaofeng@hotmail.com.
Abstract
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.
OBJECTIVE: The aim of this study was to explore the expression and biological role of miR-370-3p in humangliomas. METHODS: Clinical specimens from the brains of 20 gliomapatients 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.