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  • Title: Research on miR-126 in glioma targeted regulation of PTEN/PI3K/Akt and MDM2-p53 pathways.
    Author: Chen SR, Cai WP, Dai XJ, Guo AS, Chen HP, Lin GS, Lin RS.
    Journal: Eur Rev Med Pharmacol Sci; 2019 Apr; 23(8):3461-3470. PubMed ID: 31081101.
    Abstract:
    OBJECTIVE: 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. PATIENTS AND METHODS: 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: 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. CONCLUSIONS: 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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