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

Journal of Experimental & Clinical Cancer Research

Hong Sun¹  Yanhua Du¹  Jun Wu²  Han Liu²  Xiang Xu²  Siang Lv³ 

[1] Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University;Department of Laboratory Medicine, Shanghai General Hospital Jiading Branch, Shanghai Jiao Tong University School of Medicine;Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities;

关键词: SOCS7;    HuR;    FOXM1;    High-grade serous ovarian carcinoma;    Prognosis;   

DOI  :  10.1186/s13046-022-02395-1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown