The miR‐29 family members induce glioblastoma cell apoptosis by targeting cell division cycle 42 in a p53‐dependent manner

Abstract

AbstractBackgroundEmerging evidence has shown that miR‐29 is a promising biomarker and therapeutic target for malignancies. The roles of miR‐29a/b/c in glioma pathogenesis remain need further investigation.MethodsThe expression levels of miR‐29a/b/c and CDC42 were systematically analysed, and prognostic significance was evaluated by Kaplan–Meier survival and Cox regression analyses. The roles of miR‐29a/b/c in apoptosis and the underlying mechanisms were explored via an alkaline single‐cell gel electrophoresis assay, caspase 3/7 activity assays and Western blotting.ResultsmiR‐29a/b/c expression decreased progressively with the elevation of the WHO grade in our 147 human glioma specimens, compared with 20 non‐tumour control brain tissues, and decreased miR‐29a/b/c expression was associated with more aggressive phenotypes. Kaplan–Meier and Cox regression analyses demonstrated that lower miR‐29a/b/c expression was correlated with worse prognosis, which was confirmed by analysis of 198 glioma patients from the CGGA cohort. These all indicate that miR‐29a/b/c were independent predictors of prognosis in glioma patients. miR‐29a/b/c induced apoptosis in GBM cells by silencing CDC42. Further detailed mechanistic investigation revealed that miR‐29a/b/c promoted apoptosis in a p53‐dependent manner by suppressing the CDC42/PAK/AKT/MDM2 pathway.ConclusionsmiR‐29a/b/c are independent predictors of prognosis in glioma patients. They induce glioblastoma cell apoptosis via silencing of CDC42 and suppression of downstream PAK/AKT/MDM2 signalling in a p53‐dependent manner.