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Epigenetic reprogramming in hepatic carcinogenesis

ABSTRACT: Genomic sequencing of hepatocellular carcinoma (HCC) uncovers a paucity of actionable mutations, underscoring the necessity to exploit epigenetic vulnerabilities for therapeutics. In HCC, EZH2-mediated H3K27me3 represents a major oncogenic chromatin modification, but how it modulates the therapeutic vulnerability of signaling pathways remains unknown. Here, we identified that EZH2 maintains H3K27 methylome through epigenetic silencing of specific gene sets. ChIP-seq revealed enrichment of EZH2/H3K27me3 at silenced loci in HBx-transgenic (TG) mouse-derived HCCs, including tumor suppressors whose down-regulation significantly correlated with EZH2 overexpression and poor survival of HCC patients. Defining the aberrant chromatin landscape of HCC sheds light into the mechanistic basis of effective EZH2-targeted inhibition.

ORGANISM(S): Mus musculus

PROVIDER: GSE113326 | GEO | 2018/07/02

REPOSITORIES: GEO

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