ArticleExperimental & molecular medicine2025
KLF6-mediated recruitment of the p300 complex enhances H3K23su and cooperatively upregulates SEMA3C with FOSL2 to drive 5-FU resistance in colon cancer cells.
Article in Experimental & molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- SDC1Gut · 2026Article
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Natural Plant Bioactives as Regulators of Histone Modifications: Bridging Epigenetics and Anticancer Therapy.Phytotherapy research : PTR · 2026Review
- Novel protein acylations in Alzheimer's disease: Molecular, mechanisms, biological significance, and diagnostic and therapeutic potentials.Journal of advanced research · 2026Review
- The impact of microbial metabolites on host chromatin and epigenetic regulation.Nature metabolism · 2026Review
- Stage-Specific H3K14 and H3K23 Succinylation Orchestrates Insect Metamorphosis and Oogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Succinylation in cancer immunotherapy: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
- Excessive DNA Double-Strand Breaks-Associated 3D Genome Reorganization Contributes to Neural Tube Defects with Folate Deficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Regulators of Cancer Progression: Succinylation.Cancers · 2025Review
- Targeting AKR1B1 inhibits metabolic reprogramming to reverse systemic therapy resistance in hepatocellular carcinoma.Signal transduction and targeted therapy · 2025Article
- Mitochondrial Quality Control in Bovine Oocyte Maturation: Mechanisms, Challenges, and Prospects for Enhancing Reproductive Efficiency.Animals : an open access journal from MDPI · 2025Review
- Ethnicity-Specific Molecular Alterations in MAPK and JAK/STAT Pathways in Early-Onset Colorectal Cancer.Cancers · 2025Article
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7 authors.
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Abstract
Histone lysine succinylation, an emerging epigenetic marker, has been implicated in diverse cellular functions, yet its role in cancer drug resistance is not well understood. Here we investigated the genome-wide alterations in histone 3 lysine 23 succinylation (H3K23su) and its impact on gene expression in 5-fluorouracil (5-FU)-resistant HCT15 colon cancer cells. We utilized CUT&Tag assays to identify differentially enriched regions (DERs) of H3K23su in 5-FU-resistant HCT15 cells via integration with ATAC-seq and RNA sequencing data. The regulatory network involving transcription factors (TFs), notably FOSL2 and KLF6, and their downstream target genes was dissected using motif enrichment analysis and chromatin immunoprecipitation assays. Our results revealed a strong positive correlation between H3K23su DERs, differentially expressed genes (DEGs) and H3K27ac, indicating that H3K23su enrichment is closely related to gene activation. The DEGs associated with the H3K23su GAIN regions were significantly enriched in pathways related to colorectal cancer, including the Wnt, MAPK and p53 signaling pathways. FOSL2 and KLF6 emerged as pivotal TFs potentially modulating DEGs associated with H3K23su DERs and were found to be essential for sustaining 5-FU resistance. Notably, we discovered that FOSL2 and KLF6 recruit the PCAF-p300/CBP complex to synergistically regulate SEMA3C expression, which subsequently modulates the canonical Wnt-β-catenin signaling pathway, leading to the upregulation of MYC and FOSL2. This study demonstrated that H3K23su is a critical epigenetic determinant of 5-FU resistance in colon cancer cells, exerting its effects through the modulation of critical genes and TFs. These findings indicate that interventions aimed at targeting TFs or enzymes involved in H3K23su modification could represent potential therapeutic strategies for treating colorectal cancers that are resistant to 5-FU treatment.
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