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RNA-seq study using Karpas422 xenograft tumors after vehicle or PRC2 inhibitor C36 treatment

ABSTRACT: Polycomb Repressive Complex 2 (PRC2) is the conserved methyltransferase depositing mono-, di-, and tri- methylation (H3K27me1/me2/me3) on the lysine 27 of histone H3 and thereby represses gene transcription. EZH2 is the catalytic subunit of the histone methyltransferase Polycomb Repressive Complex 2 (PRC2), and EZH2 somatic gain-of-function (GoF) mutations are lymphoma-drivers. Therefore, EZH2/PRC2 is a critical target for cancer drug development. In the present study, we characterized a small molecule inhibitor of PRC2, C36, and demonstrated its novel allosteric inhibitory mechanism from biochemical and structural perspectives. C36 efficiently inhibits H3K27 trimethylation and specifically prevents the expression of PRC2 target genes in human tumor cell lines and xenograft tumor model. And through transcriptomic and proteomic studies critical pathways regulated by PRC2 inhibition were elucidated in B cell lymphoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281570 | GEO | 2026/06/23

REPOSITORIES: GEO

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