MiR-429 induces apoptosis of glioblastoma cell through Bcl-2.

Abstract

An essential role of microRNAs (miRNAs) has been acknowledged in the tumorigenesis of glioblastoma multiforme (GBM). Very recently, miR-429 was reported to have a potential of suppressing cancer growth. However, whether miR-429 may similarly regulate growth of GBM remains unknown. Here, we analyzed the levels of miR-429 and anti-apoptotic protein Bcl-2 in GBM specimens. We combined bioinformatics analyses and luciferase reporter assay to determine the relationship between miR-429 and Bcl-2 in GBM cells. Cell survival upon temozolomide treatment was analyzed in a CCK assay. Cell apoptosis was measured by fluorescein isothiocyanate (FITC) Annexin V apoptosis detection assay. We found that miR-429 levels were significantly decreased and Bcl-2 levels were significantly increased in GBM specimens, compared to the paired adjacent non-tumor brain tissue. Moreover, the levels of miR-429 and Bcl-2 inversely correlated. Low-miR-429 subjects had an overall inferior survival, compared to high-miR-429 subjects. MiR-429 targeted the 3'-UTR of Bcl-2 mRNA to inhibit its translation. Overexpression of miR-429 inhibited Bcl-2-mediated cell survival against temozolomide-induced apoptosis, while depletion of miR-429 augmented it. Together, our data suggest that miR-429 suppression in GBM promotes Bcl-2-mediated cancer cell survival against chemotherapy-induced cell death. Re-expression of miR-429 levels in GBM cells may improve the outcome of chemotherapy.