2. Academic Validation
  3. Integrative Proteomics and Histone PTMomics Study on Anti-TNBC Effect of JIB-04

Integrative Proteomics and Histone PTMomics Study on Anti-TNBC Effect of JIB-04

  • J Am Soc Mass Spectrom. 2025 Aug 6;36(8):1609-1620. doi: 10.1021/jasms.5c00022.
Shengna Tao 1 2,  Jingli Guo 2 3,  Jingdan Zhang 4 5,  Mingya Zhang 2,  Zhe Wang 6,  Jun Zhang 2 3,  Mingjun Li 7,  Bin Liu 1,  Jian Yuan 6,  Minjia Tan 2 3 4 5,  Wensi Zhao 7
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China.
  • 2 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 3 University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4 School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 5 Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.
  • 6 State Key Laboratory of Cardiology and Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
  • 7 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University Shanghai 200433, China.
PMID: 40598877 DOI: 10.1021/jasms.5c00022
Abstract

The incidence of malignant breast Cancer is increasing, and triple-negative breast Cancer (TNBC) is particularly challenging due to its poor prognosis and limited response to conventional treatments. Recently, epigenetic inhibitors have emerged as promising therapeutic strategies for TNBC. JIB-04, that targeted histone lysine demethylases (KDMs), was reported to show Anticancer activities against TNBC. However, the molecular mechanism underlying the antitumor effect of JIB-04 remains elusive. Herein, we integrated histone PTMomics and quantitative proteomics to comprehensively characterize histone PTM site changes and signaling pathway alterations. Under JIB-04 treatment, a total of 14 significantly altered histone PTM sites were identified, including previously reported sites (H3K9me2, H3K9me3, and H3K36me3) and two newly reported sites (H3K79me2 and H3K9ac). Proteomic analysis quantified 904 differentially expressed proteins, including 495 upregulated and 409 downregulated proteins. Pathway enrichment analysis suggested that JIB-04 significantly affected the DNA damage response. Further biological evidence demonstrated that JIB-04 modulated DNA damage response, cell cycle arrest, and Apoptosis. In summary, our study provides new mechanistic insights into the Anticancer activity of JIB-04 and offers new options for the treatment of TNBC.

Keywords

JIB-04; Proteomics; TNBC; epigenetic inhibitor; histone PTMomics.

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