2. Academic Validation
  3. HDAC2 promotes colorectal tumorigenesis by triggering dysregulation of lipid metabolism through YAP1

HDAC2 promotes colorectal tumorigenesis by triggering dysregulation of lipid metabolism through YAP1

  • Cell Signal. 2025 Apr:128:111627. doi: 10.1016/j.cellsig.2025.111627.
Zhanghan Chen 1,  Weifeng Hong 2,  Bing Li 1,  Dongli He 3,  Zhong Ren 1,  Mingyan Cai 1,  Yirong Cheng 1,  Jingyi Liu 1,  Enpan Xu 1,  Yanyun Du 1,  Yuelun Dong 1,  Shilun Cai 1,  Qiang Shi 1,  Zhipeng Qi 4,  Yunshi Zhong 5
Affiliations

Affiliations

  • 1 Endoscopy Center, Zhongshan Hospital of Fudan University, Shanghai 200032, China; Endoscopy Research Institute of Fudan University, Shanghai 200032, China.
  • 2 Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310005, China; Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou 310000, China; Zhejiang Key Laboratory of Radiation Oncology, Hangzhou 310000, China.
  • 3 Department of internal medicine of Xuhui Hospital, Affiliated Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 4 Endoscopy Center, Zhongshan Hospital of Fudan University, Shanghai 200032, China; Endoscopy Research Institute of Fudan University, Shanghai 200032, China. Electronic address: qi.zhipeng@zs-hospital.sh.cn.
  • 5 Endoscopy Center, Zhongshan Hospital of Fudan University, Shanghai 200032, China; Endoscopy Research Institute of Fudan University, Shanghai 200032, China. Electronic address: zhong.yunshi@zs-hospital.sh.cn.
PMID: 39875048 DOI: 10.1016/j.cellsig.2025.111627
Abstract

Dysfunction of lipid metabolism is important for the development and progression of colorectal Cancer, but the underlying mechanisms remain unclear. Here, HDAC2 was identified as highly expressed in both adenoma and colorectal Cancer. We aimed to explore the roles and mechanisms of HDAC2 in lipid metabolism in colorectal Cancer. HDAC2 expression in adenoma and colorectal Cancer tissues was measured using tissue arrays. The function of HDAC2/YAP1 was identified using in vitro and in vivo experiments. Coimmunoprecipitation experiments, DNA pull-down assays, luciferase analyses, and ChIP-qPCR (Chromatin Immunoprecipitation-quantitative real-time polymerase chain reaction) assays were used to identify the potential mechanisms of HDAC2. We found that HDAC2 can disrupt lipid metabolism in colorectal Cancer by mediating the deacetylation of YAP1. Mechanistically, HDAC2 can bind to YAP1 and mediate deacetylation of the K280 site of YAP1. Furthermore, the deacetylation of YAP1 reduces the efficiency of its binding to the ZMYND11 promoter region, exacerbating lipid metabolism disorders, which in turn reduce lipid accumulation and increase lipid catabolism in colorectal Cancer cells. Our study identified a novel regulatory mechanism of lipid metabolism in colorectal Cancer in which HDAC2 increases lipid catabolism by regulating the deacetylation of the K280 site of YAP1, revealing that HDAC2 promotes tumor progression through the regulation of lipid metabolism.

Keywords

Colorectal cancer; HDAC2; Lipid metabolism; YAP1.

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