STMC-01. NANOPARTICLE DELIVERY OF miRNAs TO INHIBIT GBM STEM CELLS

Cancer cells arise from multiple complementary genomic and epigenomic abnormalities that deregulate pathways that control cell proliferation and tissue homeostasis. Epigenetic modifications, involving deregulation of non-coding RNAs, are emerging as critical determinants of gene expression and essential drivers of neoplastic phenotypes. Our knowledge of how these complex epigenetic mechanisms operate in the context of cancer cell phenotype regulation remains limited. Non-coding RNAs, in particular miRNAs, are emerging as critical epigenetic regulators of cell fate and oncogenesis. MiRNAs act by selectively inhibiting gene expression primarily by targeting mRNA for degradation usually via complementary 3’-UTR seed sequences. Numerous miRNAs have been found to regulate tumorigenesis and cancer cell stemness by virtue of their capacity to target tumor-suppressing or tumor promoting transcripts. We recently showed that the coordinated actions of Oct4 and Sox2 induce a tumor-propagating stem-like state in GBM cells through a mechanism that involves the induction of DNMTs and down-regulation of a network of miRNAs through promoter DNA methylation. Two of the miRNAs repressed by Oct4/Sox2, miR-148a and miR-296-5p, efficiently inhibit the tumor propagating capacity of GBM stem-like, making them excellent candidates for therapeutic intervention. Recent developments in nanomedicine provide new and exciting opportunities to treat and manage brain tumors. Cationic polymers are a cl...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: STEM CELLS Source Type: research