ENY2 promotes hepatocellular carcinoma progression via CSN5-mediated regulation of HDAC11 and FOXO1 signaling

• ENY2 is highly expressed in HCC tissues and cells, significantly correlating with poor patient prognosis, and promotes cell proliferation, migration, and invasion. • ENY2 regulates CSN5 expression through H3K9 acetylation, unveiling its epigenetic regulatory mechanism. • ENY2 stabilizes HDAC11 via CSN5-mediated deubiquitylation, enhancing HDAC11 protein levels. • HDAC11 suppresses FOXO1 expression in HCC by promoting its deacetylation and subsequent ubiquitination, thereby enhancing glycolysis and contributing to tumor progression. • FT895, a selective HDAC11 inhibitor, exhibits therapeutic potential by targeting HDAC11, restoring FOXO1 activity and suppressing HCC progression both in vitro and in vivo .