USP39 facilitates breast cancer cell proliferation through stabilization of FOXM1

Zhenwang Zhang; Wu Liu; Xiajun Bao; Tian Sun; Jiawei Wang; Mengxi Li; Chao Liu

USP39 facilitates breast cancer cell proliferation through stabilization of FOXM1

Am J Cancer Res. 2022 Aug 15;12(8):3644-3661. eCollection 2022.

Authors

Zhenwang Zhang^{1

2}, Wu Liu^{1

2}, Xiajun Bao^{1

2}, Tian Sun^{1

2}, Jiawei Wang^{1

2}, Mengxi Li³, Chao Liu^{1

2}

Affiliations

¹ Medicine Research Institute/Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Hubei University of Science and Technology Xianning 437000, Hubei, China.
² Hubei University of Science and Technology of Medicine, Xianning Medical College Xianning 437000, Hubei, China.
³ Science and Technology Industry Management Office, Hubei University of Science and Technology Xianning 437000, Hubei, China.

PMID: 36119839
PMCID: PMC9442023

Abstract

Deubiquitinating enzyme dysregulation has been linked to the development of a variety of human malignancies, including breast cancer. However, the exact involvement of the deubiquitinating enzyme USP39 in the progression of breast cancer is yet unknown. Cell viability and colony formation analysis was used to assess the effects of USP39 knockdown on breast cancer cells in this study. The interaction between USP39 and FOXM1 was investigated using co-immunoprecipitation (co-IP) and in vitro deubiquitination analysis. The expression of USP39 and FOXM1 in breast cancer tissues was studied using the TCGA database. According to our findings, USP39 deubiquitinates and stabilizes FOXM1, promoting breast cancer cell proliferation, colony formation, and tumor growth in vivo. Furthermore, elevated USP39 expression lowers FOXM1 ubiquitination, resulting in increased transcriptional activity. In addition, the high expression of USP39 reduces the ubiquitination of FOXM1, thereby enhancing the transcriptional activity of FOXM1 and regulating the expression of downstream genes Cdc25b and Plk1. USP39 is positively correlated with the expression level of FOXM1 in breast cancer cells. In general, our research revealed the USP39-FOXM1 axis as a critical driver of breast cancer cell proliferation and provided a theoretical foundation for targeting the USP39-FOXM1 axis for pancreatic cancer treatment.

Keywords: Breast cancer; cell proliferation; transcription factor FOXM1; ubiquitin-specific protease 39.