SOCS7/HuR/FOXM1 signaling axis inhibited high-grade serous ovarian carcinoma progression.

Abstract

BACKGROUND:

High-grade serous ovarian carcinoma (HGSOC) is clinically dominant and accounts for ~ 80% deaths in all types of ovarian cancer. The delayed diagnosis, rapid development, and wide dissemination of HGSOC collectively contribute to its high mortality rate and poor prognosis in the patients. Suppressors of cytokine signaling 7 (SOCS7) can regulate cytokine signaling and participate in cell cycle arrest and regulation of cell proliferation, which might also be involved in carcinogenesis. Here, we designated to investigate the functions and mechanisms of SOCS7 in HGSOC.

METHODS:

The clinical correlation between SOCS7 and HGSOC was examined by both bioinformatics and analysis of tissue samples in patients. Gain/Loss-of-function examinations were carried out to assess the effectiveness of SOCS7 in cell viability, cell cycle, and tumor growth of HGSOC. Furthermore, the underlying mechanisms were explored by identifying the downstream proteins and their interactions via proteomics analysis and immunoprecipitation.

RESULTS:

The expression of SOCS7, which was decreased in HGSOC tissues, was correlated with the clinical pathologic characteristics and overall survival of HGSOC patients. SOCS7 acted as a HGSOC suppressor by inhibiting cancer cell viability and tumor growth in vivo. The anti-HGSOC mechanism involves SOCS7's regulatory effect on HuR by mediating its ubiquitination, the regulation of FOXM1 mRNA by HuR, as well as the interplays among these three clinically relevant factors.

CONCLUSIONS:

The SOCS7 correlates with HGSOC and suppresses its tumorigenesis through regulating HuR and FOXM1, which also suggests that SOCS7 is a prospective biomarker for the clinical management of ovarian cancer, especially HGSOC.

• Authors: Yanhua Du, Xiang Xu, Siang Lv, Han Liu, Hong Sun, Jun Wu
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 41 Issue 1 Pg. 185 (May 27 2022) ISSN: 1756-9966 [Electronic] England
• PMID: 35624501 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Cytokines
• FOXM1 protein, human
• Forkhead Box Protein M1

Topics

• Carcinogenesis
• Carcinoma, Ovarian Epithelial
• Cell Line, Tumor
• Cytokines
• Female
• Forkhead Box Protein M1 (genetics, metabolism)
• Humans
• Ovarian Neoplasms (pathology)
• Prospective Studies