Glioblastoma stem cells differentiation through epigenetic modulation is driven by miR-296-5p/HMGA1/Sox2 axis

Glioma Stem Cells (GSCs) biology is finely regulated by a cross-talk of epigenetic mechanisms of regulation and the action of Oct4/Sox2 stemness gene drivers. Recently, a novel mechanism of regulation of miRNA-296-5p/Sox2 axis together with a new gene target (HMGA1) was described. The results raised questions of great relevance in glioma therapy, especially for the failure of the current radio/chemotherapies. Can miR-296-5p/HMGA1/Sox2 axis trigger the differentiation of GSCs subpopulation? Can these findings be used in a short term to develop novel therapeutics to fight glioma? We thus believe that targeting HMGA1 in GSCs, via nano-liposomes miRNA delivery together with epigenetic drugs, could overcome the failure of the current therapies. Additionally, in silico analyses to identify other gene targets of miR-296-5p with data available in literature, found a remarkable association with new gene targets whose functions are related to cell differentiation processes. Taken altogether these findings make miR-296-5p an attractive target for human brain cancer treatment.