2. Academic Validation
  3. Targeting MYOF suppresses pancreatic ductal adenocarcinoma progression by inhibiting ILF3-LCN2 signaling through disrupting OTUB1-mediated deubiquitination of ILF3

Targeting MYOF suppresses pancreatic ductal adenocarcinoma progression by inhibiting ILF3-LCN2 signaling through disrupting OTUB1-mediated deubiquitination of ILF3

  • Redox Biol. 2025 Jul:84:103665. doi: 10.1016/j.redox.2025.103665.
Zhihui Li 1,  Jianlei Zhang 1,  Jiang Yin 1,  Wen Ma 1,  Hongfan Liao 1,  Lv Ling 1,  Qingfeng Zou 1,  Yabing Cao 2,  Ying Song 1,  Guopei Zheng 1,  Xiaoye Hu 3,  Guohua Yang 4,  Nan Li 5
Affiliations

Affiliations

  • 1 Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University; Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China.
  • 2 Kiang Wu Hospital, Macao Special Administrative Region of China.
  • 3 Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University; Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China. Electronic address: hxiaoye@126.com.
  • 4 Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University; Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China. Electronic address: yangguohuadr@163.com.
  • 5 Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University; Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China. Electronic address: Linan_gz2013@163.com.
PMID: 40381229 DOI: 10.1016/j.redox.2025.103665
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is still a highly aggressive and fatal disease. The molecular mechanisms for PDAC progression are still not fully understood. Here, we demonstrated the overexpression of MYOF in PDAC in multiple sample sets, which is significantly associated with poor outcome of PDAC patients. MYOF knockout suppresses PDAC progression in vitro and in vivo. MYOF knockout exerts its effects by promoting Ferroptosis via downregulating LCN2 expression. Ectopic LCN2 expression overcame the effects of MYOF knockout in PDAC cells. Mechanistically, MYOF respectively recruits OTUB1 and ILF3 to enhance their interaction and relieves ILF3 protein ubiquitination and degradtion. MYOF maintains ILF3 protein stability, thereby enhances ILF3 interacting with and improving LCN2 mRNA stability. Moreover, we screened and identified natural compound Picroside II potentially targets MYOF to suppress PDAC progression. These findings uncover the biological roles and mechanisms of MYOF and preliminarily indicate the potential of targeting MYOF in PDAC progression, highlighting a novel therapeutic strategy for PDAC.

Keywords

Ferroptosis; ILF3; LCN2; MYOF; OTUB1; Pancreatic cancer.

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