本文采用的英格恩产品: Entranster-H4000

Neddylation-dependent LSD1 destabilization inhibits the stemness and chemoresistance of gastric cancer

Yan-Jia Guo  ¹ , Jing-Ru Pang  ² , Yu Zhang  ² , Zhong-Rui Li  ² , Xiao-Lin Zi  ³ , Hong-Min Liu  ⁴ , Ning Wang  ⁵ , Li-Juan Zhao  ⁴ , Ya Gao  ⁴ , Bo Wang  ⁴ , Piet Herdewijn  ⁶ , Cheng-Yun Jin  ⁷ , Ying Liu  ⁸ , Yi-Chao Zheng  ⁹

Affiliations

• PMID: 37689288
• DOI: 10.1016/j.ijbiomac.2023.126801

Affiliations

• ¹ Henan Key Laboratory of Precision Clinical Pharmacy, Academy of Medical Sciences, Zhengzhou University, Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, XNA platform, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
• ² Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, XNA platform, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
• ³ Department of Urology, University of California, Irvine, CA, USA; Department of Pharmacology, University of California, Irvine, CA, USA.
• ⁴ Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, XNA platform, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Academy of Medical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China.
• ⁵ The School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
• ⁶ Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, XNA platform, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China; Rega Institute for Medical Research, Medicinal Chemistry, KU Leuven, Herestraat 49-Box 1041, 3000 Leuven, Belgium.
• ⁷ Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, XNA platform, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China. Electronic address: cyjin@zzu.edu.cn.
• ⁸ Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Application & Translation of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China. Electronic address: 991536786@qq.com.
• ⁹ Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, XNA platform, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Academy of Medical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China. Electronic address: yichaozheng@zzu.edu.cn.

• PMID: 37689288
• DOI: 10.1016/j.ijbiomac.2023.126801

Abstract

Histone lysine-specific demethylase 1 (LSD1) expression has been evaluated in multiple tumors, including gastric cancer (GC). However, the mechanisms underlying LSD1 dysregulation in GC remain largely unclear. In this study, neural precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) was identified to be conjugated to LSD1 at K63 by ubiquitin-conjugating enzyme E2 M (UBE2M), and this neddylated LSD1 could promote LSD1 ubiquitination and degradation, leading to a decrease of GC cell stemness and chemoresistance. Herein, our findings revealed a novel mechanism of LSD1 neddylation and its contribution to decreasing GC cell stemness and chemoresistance. Taken together, our findings may whistle about the future application of neddylation inhibitors.

Keywords: Gastric cancer; LSD1; Neddylation; Stemness; UBE2M.