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CCDC7 Activates Interleukin-6 and Vascular Endothelial Growth Factor to Promote Proliferation via the JAK-STAT3 Pathway in Cervical Cancer Cells

Authors Zhou C, He X, Zeng Q, Zhang P, Wang C

Received 3 January 2020

Accepted for publication 12 May 2020

Published 30 June 2020 Volume 2020:13 Pages 6229—6244


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang

Cong Zhou,1 Xiang He,1,2,* Qi Zeng,3 Peng Zhang,4 Chun-ting Wang5,*

1Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 3Second Affiliated Hospital, Army Military Medical University, Chongqing 400037, People’s Republic of China; 4Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu 610041, People’s Republic of China; 5State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiang He
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, 610041, P. R. China, Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, No. 20, Section 3, People’s Road, Chengdu, Sichuan Province 610041, People’s Republic of China
Tel +86-18180609069
Fax +86-28-85559065
Chun-ting Wang
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, Sichuan Province 610041, People’s Republic of China
Tel +86-28-85164063
Fax +86-28-85164060

Objective: Tumor growth is one of the most lethal attributes of human malignancy. The expression of CCDC7, a novel gene which has multiple functions, has been shown to be associated with tumor growth and poor prognosis in patients with cancer. However, the specific functions of CCDC7 remain unclear. Here, we investigated the molecular mechanisms underlying the effects of CCDC7 on proliferation in cervical cancer.
Materials and Methods: The MTT and EdU assays were performed to evaluate the function of CCDC7. The immunohistochemical, quantitative real-time PCR (qRT-PCR), ELISA and Western blot assay were used to detect the gene and protein expression in tissues and cells. A xenograft test was conducted to detect the impact of CCDC7 on tumor development in vivo.
Results: In immunohistochemical analysis of 193 cases, normal cervical tissue and cervical cancer tissue show that CCDC7 expression is closely correlated with the development of cervical cancer and was positively correlated with the clinical stage and histological grade. Overexpression or knockdown of CCDC7 affected cell proliferation in cervical cancer cells in vitro. In a nude mouse xenograft model in vivo, knockdown of CCDC7 inhibited cell proliferation and tumor growth. Furthermore, CCDC7 overexpression upregulated interleukin (IL)-6 and vascular endothelial growth factor (VEGF) at mRNA and protein levels, and treatment with recombinant IL-6 or VEGF proteins also increased CCDC7 expression. In a case set of 80 patients with cervical cancer, we found that CCDC7, IL-6, and VEGF affected patient prognosis. Finally, inhibition of various signaling pathways using specific inhibitors indicated that CCDC7 blocked the decrease in cell proliferation observed following suppression of the JAK-STAT3 pathway, suggesting that CCDC7 functioned via this critical signaling network.
Conclusion: Those findings indicated that CCDC7 may be a novel target for the treatment of cervical cancer and may have applications as a predictive marker for tumor growth in cervical carcinoma.

Keywords: CCDC7, IL-6, VEGF, tumor growth, cervical cancer, gene therapy

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