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USP43 impairs cisplatin sensitivity in epithelial ovarian cancer through HDAC2-dependent regulation of Wnt/ß-catenin signaling pathway.
Pei, Lipeng; Zhao, Feng; Zhang, Yi.
Affiliation
  • Pei L; Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, Shenyang, People's Republic of China.
  • Zhao F; Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China.
  • Zhang Y; Department of Gynecology, The First Hospital of China Medical University, No. 155, Nanjing North Street, Shenyang, People's Republic of China. Syzi@163.com.
Apoptosis ; 29(1-2): 210-228, 2024 Feb.
Article in En | MEDLINE | ID: mdl-38087046
Epithelial ovarian cancer (EOC) is the leading cause of cancer death all over the world. USP43 functions as a tumor promoter in various malignant cancers. Nevertheless, the biological roles and mechanisms of USP43 in EOC remain unknown. In this study, USP43 was highly expressed in EOC tissues and cells, and high expression of USP43 were associated with a poor prognosis of EOC. USP43 overexpression promoted EOC cell proliferation, enhanced the ability of migration and invasion, decreased cisplatin sensitivity and inhibited apoptosis. Knockdown of USP43 in vitro effectively retarded above malignant progression of EOC. In vivo xenograft tumors, silencing USP43 slowed tumor growth and enhanced cisplatin sensitivity. Mechanistically, USP43 inhibited HDAC2 degradation and enhanced HDAC2 protein stability through its deubiquitylation function. USP43 diminished the sensitivity of EOC cells to cisplatin through activation of the Wnt/ß-catenin signaling pathway mediated by HDAC2. Taken together, the data in this study revealed the functions of USP43 in proliferation, migration, invasion, chemoresistance of EOC cells, and the mechanism of HDAC2-mediated Wnt/ß-catenin signaling pathway. Thus, USP43 might serve as a potential target for the control of ovarian cancer progression.
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Full text: 1 Database: MEDLINE Main subject: Ovarian Neoplasms / Cisplatin Limits: Female / Humans Language: En Year: 2024 Type: Article

Full text: 1 Database: MEDLINE Main subject: Ovarian Neoplasms / Cisplatin Limits: Female / Humans Language: En Year: 2024 Type: Article