Dual Regulation of Histone Methylation by mTOR Complexes Controls Glioblastoma Tumor Cell Growth via EZH2 and SAM.

摘要: Epigenetic regulation known for DNA methylation and histone modification is critical securing proper gene expression chromosomal function, its aberration induces various pathological conditions including cancer. Trimethylation of H3 on lysine 27 (H3K27me3) to suppress genes related cancer cell survival the level H3K27me3 may have an influence tumor progression malignancy. However, it remains unclear how regulated in response genetic mutation microenvironmental cues facilitate survival. Here, we report a novel mechanism specific by cooperatively two mechanistic target rapamycin (mTOR) complexes, mTORC1 mTORC2 human glioblastoma (GBM). Integrated analyses revealed that upregulates protein enhancer zeste homolog 2 (EZH2), main component polycomb repressive complex (PRC2) which as H3K27-specific methyltransferase. The other mTOR complex, mTORC2, regulates production S-adenosylmethionine (SAM), essential substrate methylation. This cooperative causes H3K27 hypermethylation subsequently promotes both vitro vivo xenografted mouse model. These results indicate activated complexes contribute through epigenetic regulation, nominating them exploitable therapeutic against cancer. Implications: A dynamic growth GBM, but at same time could be this deadly tumor.