HMGA1 negatively regulates NUMB expression at transcriptional and post transcriptional level in glioblastoma stem cells

ABSTRACTGlioblastoma (GBM) is a lethal, fast-growing brain cancer, affecting 2–3 per 100,000 adults per year. It arises from multipotent neural stem cellswhich have reduced their ability to divide asymmetrically and hence divide symmetrically, generating increasing number of cancer stem cells, fostering tumor growth.We have previously demonstrated that the architectural transcription factor HMGA1is highly expressed in brain tumor stem cells (BTSCs) and that its silencing increases stem cell quiescence, reduces self-renewal and sphere-forming efficiency in serial passages, suggesting a shift from symmetric to asymmetric division. Since NUMBexpression is fundamental for the fulfillment of asymmetric division in stem cells, and is lost or reduced in many tumors, including GBM, we have investigated the ability of HMGA1to regulate NUMBexpression. Here, we show that HMGA1negatively regulates NUMBexpression at transcriptional level, by binding its promoter and counteracting c/EBP-β and at posttranscriptio...