Tumoral RCOR2 promotes tumor development through dual epigenetic regulation of tumor plasticity and immunogenicity.

ABSTRACT: Gain of plasticity and loss of MHC-II enable tumor cells to evade immune surveillance, contributing to tumor development. Here, we showed that the transcriptional corepressor RCOR2 is a key factor that integrates two epigenetic programs surveilling tumor plasticity and immunogenicity. RCOR2 was upregulated predominantly in tumor cells and promoted tumor development in mice through reducing tumor cell death by CD4+CD8+ T cells and inducing cancer stemness. Mechanistically, RCOR2 repressed RNF43 expression through LSD1-mediated demethylation of histone H3 at lysine 4 to induce activation of Wnt/β-catenin and tumor stemness. Simultaneously, RCOR2 inhibited CIITA expression through HDAC1/2-mediated deacetylation of histone H4 at lysine 16, leading to MHC-II silencing in tumor cells and subsequ

SUBMITTER: Bao L 

PROVIDER: S-EPMC12435851 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature