PRMT2 links H3R8me2a to oncogenic activation. Homo sapiens

Here we find that PRMT2 is highly expressed in GBM and correlated with poor prognosis. The downregulation of PRMT2 inhibits GBM cell growth, and glioblastoma stem cells self-renewal in vitro and abrogates orthotopic tumor growth. Transcriptome analysis demonstrate that PRMT2 depletion leads to significant deregulation of genes mainly associated with cell cycle progression and pathways in cancer. And we confirm that PRMT2 is responsible for the H3R8 asymmetric methylation (H3R8me2a). Chromatin Immunoprecipitation sequencing analyses show that H3R8me2a is closely correlated with known active histone marks. And PRMT2-mediated H3R8me2a is required for the maintenance of target gene expression and the active histone modification levels at their enhancers and promoters. Consistently, the expression of catalytically inactive mutant of PRMT2 disrupts its protumorigenic functions. Therefore this study demonstrates that PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in GBM pathogenesis and provides a rationale for PRMT2 targeting in aggressive gliomas.