STMC-12. Sox2 ACTIVATES THE EXPRESSION OF ONCO-miRNA-486-5p

In this study, we identify miRNA-486-5p as a Sox2-induced miRNA that regulates GBM SC self-renewal, through its inhibition of the tumor suppressor gene, FoxO1. Using established glioma cell lines and patient-derived neurospheres as models of GBM, we show that miR-486-5p associates with the GBM SC phenotype and is directly induced by Sox2. Forced expression of miR-486-5p in vitro enhances the self-renewal capacity of GBM neurospheres and inhibition of endogenous miR-486-5p leads to cell death, concomitant with the activation of the miRNA-486-5p target FoxO1. These results suggest that Sox2 regulates the survival of GBM stem cells, in part by activating miR-486-5p and repressing FoxO1, thereby preventing apoptosis of glioblastoma cells. The Sox2: miRNA-486-5p: FoxO1 axis offers a new target for therapies aiming to deplete GBM of its stem-like subset of cells responsible for malignancy and poor prognoses.
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: STEM CELLS Source Type: research