HMGA2 promotes glioma invasion and poor prognosis via a long-range chromatin interaction

Abstract

To identify the function and underlying mechanisms of HMGA2 on the prognosis and invasion of gliomas, HMGA2 was detected by immunohistochemistry. The Kaplan-Meier and Cox's regression analysis results showed that higher HMGA2 level predicted the poorer outcomes of glioma patients. ChIP-qPCR, DNA electrophoretic mobility shift assay, chromosome conformation capture, and co-immunoprecipitation were applied to identify HMGA2-activated target sites, which were further verified by mRNA and protein expression detection. Transwell and orthotopic implantation were used to investigate the roles of HMGA2 in glioma cells. HMGA2 shRNA transfection inhibited glioblastoma invasion. Mechanistically, we first discovered that HMGA2, together with GCN5, facilitated the invasion of glioma cells via inducing chromatin conformational remodeling of the MMP2 gene promoter and epigenetically activating MMP2 gene transcription. Our results indicated that HMGA2, as a novel GCN5 recognition partner and histone acetylation modulator, may be novel prognostic indicator and promising glioma treatment target.