ACTL6A Depletion Induces KLF4-Mediated Anti-Tumorigenic Effects in Colorectal Cancer
ACTL6A, a critical subunit of the SWI/SNF and INO80 chromatin-remodeling complexes, is frequently overexpressed in cancers, including colorectal cancer (CRC). This study investigates the epigenetic mechanisms by which ACTL6A depletion reduces CRC cell proliferation. A multi-omics approach reveals that ACTL6A deficiency alters chromatin accessibility and promotes the expression of P53 pathway-related genes. This is accompanied by enhanced KLF4 binding at newly accessible genomic sites, which correlates with increased transcriptional activation. KLF4 co-localizes with SWI/SNF and INO80 complexes, driving chromatin remodeling and transcriptional activation of genes associated with cell death. The findings suggest that ACTL6A represses KLF4 activity to promote tumor proliferation and identifies potential therapeutic strategies targeting ACTL6A in CRC.