2. Academic Validation
  3. NSD2 methylates AROS to promote SIRT1 activation and regulates fatty acid metabolism-mediated cancer radiotherapy

NSD2 methylates AROS to promote SIRT1 activation and regulates fatty acid metabolism-mediated cancer radiotherapy

  • Cell Rep. 2023 Oct 31;42(10):113126. doi: 10.1016/j.celrep.2023.113126.
Xun Li 1,  Da Song 2,  Yaqi Chen 2,  Changsheng Huang 2,  Anyi Liu 2,  Qi Wu 2,  Xiaowei She 2,  Kangdi Li 2,  Kairui Wan 2,  Chengxin Yu 2,  Cheng Qiu 2,  Lang Liu 2,  Guihua Wang 2,  Feng Xu 2,  Jing Wang 3,  Junbo Hu 4
Affiliations

Affiliations

  • 1 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, P.R. China; Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
  • 2 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
  • 3 Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China. Electronic address: wangjhxh@163.com.
  • 4 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, P.R. China. Electronic address: jbhu@tjh.tjmu.edu.cn.
PMID: 37756162 DOI: 10.1016/j.celrep.2023.113126
Abstract

Fatty acid metabolism plays a critical role in both tumorigenesis and Cancer radiotherapy. However, the regulatory mechanism of fatty acid metabolism has not been fully elucidated. NSD2, a Histone Methyltransferase that catalyzes di-methylation of histone H3 at lysine 36, has been shown to play an essential role in tumorigenesis and Cancer progression. Here, we show that NSD2 promotes fatty acid oxidation (FAO) by methylating AROS (active regulator of SIRT1) at lysine 27, facilitating the physical interaction between AROS and SIRT1. The mutation of lysine 27 to arginine weakens the interaction between AROS and SIRT1 and impairs AROS-SIRT1-mediated FAO. Additionally, we examine the effect of NSD2 inhibition on radiotherapy efficacy and find an enhanced effectiveness of radiotherapy. Together, our findings identify a NSD2-dependent methylation regulation pattern of the AROS-SIRT1 axis, suggesting that NSD2 inhibition may be a potential adjunct for tumor radiotherapy.

Keywords

AROS methylation; CP: Cancer; CP: Metabolism; NSD2; SIRT1; fatty acid metabolism; radiotherapy.

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