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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(Open Access)

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机构: [1]Key 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, China [2]Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, 610041, China [3]Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China [4]Department 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, China [5]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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关键词: CCDC7 Cervical cancer Gene therapy IL-6 Tumor growth VEGF

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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. © 2020 Zhou et al.

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出版当年[2020]版:
大类 | 3 区 医学
小类 | 3 区 生物工程与应用微生物 4 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 3 区 生物工程与应用微生物 4 区 肿瘤学
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出版当年[2020]版:
Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q3 ONCOLOGY
最新[2023]版:
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q3 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Key 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, China
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通讯机构: [1]Key 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, China [2]Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, 610041, China [5]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [*1]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 [*2]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
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