Research on miR-126 in glioma targeted regulation of PTEN/PI3K/Akt and MDM2-p53 pathways.

PTEN公司 张力素 胶质瘤 PI3K/AKT/mTOR通路 碘化丙啶 蛋白激酶B 癌症研究 细胞生长 转染 细胞凋亡 分子生物学 平方毫米 生物 MTT法 污渍 细胞培养 程序性细胞死亡 基因 生物化学 遗传学
作者
S-R Chen,W-P Cai,X-J Dai,A-S Guo,H-P Chen,G-S Lin,R.J. Lin
出处
期刊:PubMed 卷期号:23 (8): 3461-3470 被引量:37
标识
DOI:10.26355/eurrev_201904_17711
摘要

To study the correlations of micro ribonucleic acid (miR)-126 expression with pathogenesis and prognosis of glioma, and to screen potential biological targets for the diagnosis, treatment and prognosis of glioma.miR-126 expression in cancer tissues, normal brain tissues, U87MG cells and normal astrocytes in glioma patients was quantitatively analyzed via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). U87MG cells were transfected with miR-126 mimics or miR-126 inhibitor, followed by verification via qRT-PCR. The cell proliferation, apoptosis, migration and invasion after transfection were analyzed using methyl thiazolyl tetrazolium (MTT) assay, Annexin V/propidium iodide (PI) assay, wound healing assay and transwell assay, respectively. The expression levels of proteins related to phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol 3-kinase/protein kinase B (PTEN/PI3K/Akt) pathway and double mouse minute 2 homolog (MDM2)-p53 pathway were detected via Western blotting. Moreover, the prognostic analysis was performed using the Kaplan-Meier method and log-rank test.Results of qRT-PCR showed that the miR-126 expression in highly malignant glioma tissues and U87MG cells were significantly lower than those in normal brain cells, and its expression level was significantly higher or lower than that in negative control group after transfection with miR-126 mimics or inhibitor. Analyses of cell proliferation, apoptosis, migration and invasion revealed that the up-regulation of miR-126 could remarkably inhibit the in-vitro proliferation, migration and invasion and promote apoptosis of glioma cells, and vice versa. Results of Western blotting manifested that after overexpression of miR-126, PI3K, p-Akt and MDM2 protein levels in U87MG cells were significantly decreased compared with those in control group, but PTEN and p53 protein expressions were significantly increased, and vice versa. Besides, according to prognostic analysis, the prognosis of patients with a low miR-126 level was poorer.The miR-126 expression is abnormally low in glioma cells, and miR-126 inhibits the course of glioma through targeted regulation of PTEN/PI3K/Akt and MDM2-p53 pathways, which, therefore, can be used as a new potential biomarker for the diagnosis, treatment and prognosis of glioma.

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