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<p>ACTL6A, a subunit of the SWI/SNF and INO80 chromatin remodeling complexes, is frequently overexpressed in various cancers, and its depletion attenuates cell proliferation in colorectal cancer (CRC). However, the epigenetic mechanisms underlying ACTL6A function remain poorly understood. Here, we aimed to elucidate how ACTL6A regulates chromatin accessibility and gene expression in CRC. Integrated multi-omics analyses revealed that ACTL6A deficiency alters chromatin accessibility and upregulates P53 pathway-related genes, accompanied by the recruitment of SWI/SNF and INO80 complexes. Mechanistically, ACTL6A depletion enhances KLF4 binding at newly accessible regions, where it cooperates with these chromatin remodeling complexes to activate P53 pathway-related genes and induce apoptosis. ACTL6A contributes to CRC cell proliferation by inhibiting the KLF4-mediated transcriptional activation of tumor-suppressive genes. Thus, our findings highlight that targeting ACTL6A may serve as a promising therapeutic strategy in CRC.</p><p></p>

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ACTL6A depletion induces KLF4-mediated anti-tumorigenic effects in colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月28日

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  • Hye-Ju Yang,
  • Eun-Ju Kim,
  • Yeonsoo Kim,
  • Youngwon Cho,
  • Younghee Choi,
  • Sang-Hyun Song,
  • Tae-You Kim

摘要

ACTL6A, a subunit of the SWI/SNF and INO80 chromatin remodeling complexes, is frequently overexpressed in various cancers, and its depletion attenuates cell proliferation in colorectal cancer (CRC). However, the epigenetic mechanisms underlying ACTL6A function remain poorly understood. Here, we aimed to elucidate how ACTL6A regulates chromatin accessibility and gene expression in CRC. Integrated multi-omics analyses revealed that ACTL6A deficiency alters chromatin accessibility and upregulates P53 pathway-related genes, accompanied by the recruitment of SWI/SNF and INO80 complexes. Mechanistically, ACTL6A depletion enhances KLF4 binding at newly accessible regions, where it cooperates with these chromatin remodeling complexes to activate P53 pathway-related genes and induce apoptosis. ACTL6A contributes to CRC cell proliferation by inhibiting the KLF4-mediated transcriptional activation of tumor-suppressive genes. Thus, our findings highlight that targeting ACTL6A may serve as a promising therapeutic strategy in CRC.