P300-dependent acetylation of the FOXQ1 complex activates super-enhancers to promote colorectal cancer proliferation and metastasis

  • Commun Biol. 2025 Jul 7;8(1):1016. doi: 10.1038/s42003-025-08430-z.
Wen-Dong Yang  #  1 ,  Zhi-Heng Zhang  #  1 ,  Man-Yi Zhao  #  2 ,  Ke Shao  #  3 ,  Yan-Feng Ma  4 ,  Qi Shen  1 ,  Meng-Ru Lu  1 ,  Zhi-Ying Shao  1 ,  Jia-Yu Xu  2 ,  Meng-Han Cao  5 ,  Seng Meng  1 ,  Su-Fang Chu  1 ,  Hong-Mei Yong  6 ,  Jin Ding  7 ,  Jin Bai  8  9  10
Affiliations
  • 1. Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2. Department of Oncology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, Jiangsu, China.
  • 3. Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • 4. Cardiology Department, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 5. Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 6. Department of Oncology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, Jiangsu, China. [email protected].
  • 7. Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China. [email protected].
  • 8. Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 9. Cardiology Department, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • 10. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. [email protected].
  • # Contributed equally.
PMID: 40624346 DOI: 10.1038/s42003-025-08430-z
Abstract

The FOX transcription factor family plays a pivotal role in the malignant progression of Tumors. We propose a hypothesis that FOXQ1 recruits p300 and BRD4 to super-enhancer regions. Our findings indicate that p300 acetylates Lys190 of FOXQ1, resulting in its recognition and binding by BRD4. Subsequently, BRD4 recruits RNA-Pol II to form a "FOXQ1-p300-BRD4-RNA Pol II" complex, which then binds to the super-enhancers of target genes. Meanwhile, acetylation at Lys190 of FOXQ1 directly enhances its binding affinity to super-enhancers. Consequently, more target oncogenes can be transcribed to promote CRC proliferation and metastasis. Our results suggest that FOXQ1 acts as a key regulator of super-enhancers, providing insights into its role in CRC and highlighting its potential as a therapeutic target.

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