2. Academic Validation
  3. Deubiquitinating enzyme USP42 promotes breast cancer progression by inhibiting JNK/p38-mediated apoptosis

Deubiquitinating enzyme USP42 promotes breast cancer progression by inhibiting JNK/p38-mediated apoptosis

  • Sci Rep. 2025 Oct 21;15(1):36751. doi: 10.1038/s41598-025-20573-x.
Chongwu He # 1,  Jing Chen # 2,  Ruibo Tian 3,  Liu Yang 4,  Wenrui He 5,  Longbo He 1,  Jiawei Xu 6,  Jianglong Li 1,  Gongxian Wang 7,  Changan Jiang 8,  Qiang Liu 9,  Xianghua Wan 10 11,  Tenghua Yu 12 13
Affiliations

Affiliations

  • 1 Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, China.
  • 2 Department of Nursing, Nanchang Medical College, Nanchang, Jiangxi Province, China.
  • 3 Department of Thyroid and Breast Surgery, Xing'an League People's Hospital, Xing'an League, Ulanhot, Inner Mongolia Autonomous Region, China.
  • 4 Department of Pathology, Nanchang People's Hospital, Nanchang, Jiangxi Province, China.
  • 5 Department of Urology, General Hospital, Ningxia Medical University, Yinchuan, China.
  • 6 Graduate school, Nanchang University, Nanchang, Jiangxi Province, China.
  • 7 Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
  • 8 Department of General Surgery, Poyang County People's Hospital, Shangrao, Jiangxi Province, China.
  • 9 Department of Vascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
  • 10 Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, China. wanxh1996@163.com.
  • 11 Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, The Second Affiliated Hospital of Nanchang Medical College, 519 East Beijing Road, Nanchang, 330029, Jiangxi Province, China. wanxh1996@163.com.
  • 12 Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, China. yuthua2016@163.com.
  • 13 Department of Breast Surgery, Jiangxi Cancer Hospital & Institute, The Second Affiliated Hospital of Nanchang Medical College, 519 East Beijing Road, Nanchang, 330029, Jiangxi Province, China. yuthua2016@163.com.
  • # Contributed equally.
PMID: 41120683 DOI: 10.1038/s41598-025-20573-x
Abstract

This study investigated the role of ubiquitin specific peptidase 42 (USP42) in breast Cancer proliferation, focusing on its modulation of Apoptosis via the JNK/p38 signaling pathway. USP42 expression levels in breast Cancer cell lines were assessed using western blotting and RT-qPCR. In vitro, cell proliferation was evaluated using CCK-8 assay and clonogenic assay assessed, while Apoptosis was measured by flow cytometry evaluated. Western blotting was used to analyze the expression of apoptosis-related proteins and those associated with the JNK/p38 pathway. The effect of USP42 knockdown on breast Cancer cell proliferation was examined in vivo using a xenograft nude mice model. USP42 protein levels were significantly higher in breast Cancer tissues than in normal breast tissues. Moreover, USP42 expression was positively correlated with the advanced T stage, N stage, and pathological stage. USP42 knockdown in MCF7 and MDA-MB-231 cells resulted in decreased proliferation and increased Apoptosis rates. USP42 silencing upregulated Caspase-3 and Bax expression, while downregulating Bcl-2. Phosphorylation of JNK and p38 increased significantly following USP42 silencing. Treatment with SP600125 (JNK Inhibitor) or SB203580 (p38 MAPK Inhibitor) effectively recused JNK and p38 activation. Both inhibitors also reduced the apoptotic cell population, which was upregulated by USP42 silencing. These findings highlight USP42 promotes breast Cancer progression by reducing JNK and p38 activation and inhibiting Apoptosis, suggesting its potential as a therapeutic target in breast Cancer treatment.

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