miR-622 inhibits the tumorigenesis of glioblastoma through GLUT3 repression

Abstract

Histone deacetylases (HDAC) is modified histone-proteins. HDAC2 is a member of classⅠ HDAC and associated brain development. HDAC2 is highly expressed in various cancers and correlated with GBM progression. HDAC inhibitor is known to be effective in therapeutic cancer. GLUT3 is also highly expressed in GBM cells. Thus, we studied the tumorigenesis and apoptosis of GBM cells (U87MG and A172) by miR-622-regulated GLUT3 repression. miR-622 is highly correlated with apoptosis in GBM cells (U87MG and A172). MiR-622 significantly downregulated GLUT3 expression and induced apoptosis in GBM cells. Also, we showed that miR-622 suppressed the colony formation in GBM cells by colony formation assay. Additionally, we demonstrated that miR-622 induced apoptosis in GBM cells by the MTT and FACS analysis, and DNA damage by the TUNEL assay. The GBM tumor size decreased in orthotopic mouse model that was injected with miR-622. GLUT3 is essential for tumor metabolism and GLUT3 upregulation is involved in tumor progression and resistance to therapy. GLUT3-CDS was found to interact with miR-622. HDAC2 knockdown in GBM cells induces GBM cell death through miR-622 upregulation and GLUT3 downregulation. Thus, this study demonstrated that miR-622 expression in HDAC2-silenced GBM cells suppressed GLUT3 expression and induce GBM cell death.