2. Academic Validation
  3. Histone acetyltransferase KAT6A contributes to colon cancer malignant progression by inhibiting ferroptosis

Histone acetyltransferase KAT6A contributes to colon cancer malignant progression by inhibiting ferroptosis

  • BMC Cancer. 2025 Dec 27;26(1):150. doi: 10.1186/s12885-025-15368-2.
Junyu Huo 1,  Hongyuan Chen 1,  Xiaoqiao Zhang 1,  Dong Sun 2,  Hongguang Sheng 1,  Yugang Jiang 3
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
  • 2 Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250117, China.
  • 3 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China. [email protected].
PMID: 41454337 DOI: 10.1186/s12885-025-15368-2
Abstract

Background: Colon Cancer (CC) is a malignant Cancer with high incidence and poor prognosis.Ferroptosis could induce iron-dependent accumulation of lipid peroxidation and oxidative death of Cancer cells. This work aimed to elucidate the role of KAT6A, a lysine acetyltransferase, in CC development.

Methods: We collected tumor and paired non-tumor samples from patients with CC and analyzed the RNA and protein level of KAT6A using quantitative Real-Time PCR and immunohistochemistry (IHC) staining. We conducted KAT6A knockdown in CC cells and determined cell proliferation and Ferroptosis. Cell proliferation was measured by cell counting kit-8 (CCK-8) and colony formation assay. Ferroptosis was identified by measuring the levels of lipid ROS, intracellular iron and Fe2+, malondialdehyde (MDA), and glutathione (GSH). The in vivo effects of KAT6A were assessed by xenograft mouse model. Protein levels of KAT6A and Glutathione Peroxidase 4 (GPX4) were checked by western blotting assay. The enticement of acetylation on lysine 9 of histone3 (H3K9ac) and RNA polymerase II on GPX4 gene was analyzed by chromatin immunoprecipitation (ChIP) assay.

Results: The RNA and protein level of KAT6A is notably higher in tumor tissues compared with the non-tumor sections. Depletion of KAT6A suppressed in vitro and in vivo CC cell growth. Overexpression of KAT6A reversed the erastin-induced CC cell death. knockdown of KAT6A significantly elevated the intracellular level of MDA, induced accumulation of total iron, Fe2+ and lipid ROS, and suppressed the level of GSH. The knockdown of KAT6A caused a decrease in the expression of GPX4 and enrichment of H3K9ac on GPX4 gene.

Conclusion: KAT6A promotes the proliferation of CC cells and suppresses Ferroptosis via epigenetic regulation of GPX4. Our work presented KAT6A as a potential diagnostic and therapeutic target for treatment CC.

Keywords

Colon cancer; Epigenetic regulation; Ferroptosis; Glutathione peroxidase 4; Lysine acetyltransferase 6A.

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