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M2-macrophage maintenance by miRNA dysregulations in GBM. Hypoxic-derived exosomes contain miR-1246, which modulate STAT3 activity, alongside miR-21 EVs released from both GBM cells and M2-macrophages in order to support each other by STAT3 activation. miR-340-5p downregulation is a key mechanism of communication, since its downstream targets contribute both to M2 polarization and the maintenance of miR-340-5p underexpression; (arrows—activation; dotted T-bars inhibitory effect).
