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- Title
USP53 Affects the Proliferation and Apoptosis of Breast Cancer Cells by Regulating the Ubiquitination Level of ZMYND11.
- Authors
Meng, Xiangchao; Chen, Hongye; Tan, Zhihui; Yan, Weitao; Liu, Yinfeng; Lv, Ji; Han, Meng
- Abstract
Breast cancer is the most common female malignancy worldwide. Ubiquitin-specific peptidase 53 (USP53) has been shown to exert cancer-suppressing functions in several solid tumors, but its role and the underlying mechanism in breast cancer has not been clearly elucidated. Therefore, we have carried out a series of detailed studies on this matter at the levels of bioinformatics, clinical tissue, cell function and animal model. We found that USP53 expression was downregulated in breast cancer specimens and was negatively correlated with the clinical stages. Gain- and loss-of-function experiments demonstrated USP53 inhibited proliferation, clonogenesis, cell cycle and xenograft growth, as well as induced apoptosis and mitochondrial damage of breast cancer cells. Co-immunoprecipitation data suggested that USP53 interacted with zinc finger MYND-type containing 11 (ZMYND11), and catalyzed its deubiquitination and stabilization. The 33–50 amino acid Cys-box domain was key for USP53 enzyme activity, but not essential for its binding with ZMYND11. The rescue experiments revealed that the anti-tumor role of USP53 in breast cancer cells was at least partially mediated by ZMYND11. Both USP53 and ZMYND11 were prognostic protective factors for breast cancer. USP53-ZMYND11 axis may be a good potential biomarker or therapeutic target for breast cancer, which can provide novel insights into the diagnosis, treatment and prognosis. Keypoints: 1. USP53 has been shown to play an anticancer role in a variety of solid malignancies, but its role in breast cancer and its mechanism remain unclear. 2. Our results suggested that USP53 was low expressed in breast cancer and negatively correlated with TNM stage; USP53 suppressed proliferation and triggered apoptosis of breast cancer cells; USP53 inhibited breast cancer in vitro and in vivo by deubiquitinating ZMYND11. 3. USP53-ZMYND11 axis may be a potential breast cancer marker and therapeutic target.
- Subjects
CANCER cell growth; BREAST cancer; CANCER cells; DEUBIQUITINATING enzymes; UBIQUITINATION; APOPTOSIS
- Publication
Biological Procedures Online, 2024, Vol 26, Issue 1, p1
- ISSN
1480-9222
- Publication type
Article
- DOI
10.1186/s12575-024-00251-4