Zhou Cong, He Xiang, Zeng Qi, Zhang Peng, Wang Chun-Ting
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, People's Republic of China.
Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
Onco Targets Ther. 2020 Jun 30;13:6229-6244. doi: 10.2147/OTT.S244663. eCollection 2020.
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.
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 .
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.
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.
肿瘤生长是人类恶性肿瘤最致命的特征之一。CCDC7是一种具有多种功能的新基因，其表达已被证明与肿瘤生长及癌症患者的不良预后相关。然而，CCDC7的具体功能仍不清楚。在此，我们研究了CCDC7影响宫颈癌增殖的分子机制。
采用MTT和EdU试验评估CCDC7的功能。采用免疫组织化学、定量实时PCR（qRT-PCR）、酶联免疫吸附测定（ELISA）和蛋白质免疫印迹法检测组织和细胞中的基因和蛋白质表达。进行异种移植试验以检测CCDC7对体内肿瘤发展的影响。
在对193例病例的免疫组织化学分析中，正常宫颈组织和宫颈癌组织显示CCDC7表达与宫颈癌的发展密切相关，且与临床分期和组织学分级呈正相关。CCDC7的过表达或敲低影响体外宫颈癌细胞的增殖。在体内裸鼠异种移植模型中，CCDC7的敲低抑制细胞增殖和肿瘤生长。此外，CCDC7的过表达在mRNA和蛋白质水平上调白细胞介素（IL）-6和血管内皮生长因子（VEGF），用重组IL-6或VEGF蛋白处理也增加CCDC7表达。在一组80例宫颈癌患者中，我们发现CCDC7、IL-6和VEGF影响患者预后。最后，使用特异性抑制剂抑制各种信号通路表明，CCDC7阻断了JAK-STAT3通路抑制后观察到的细胞增殖下降，提示CCDC7通过这一关键信号网络发挥作用。
这些发现表明，CCDC7可能是治疗宫颈癌的新靶点，也可能作为宫颈癌肿瘤生长的预测标志物。
