Downregulation of cell division cycle-associated protein 7 (CDCA7) suppresses cell proliferation, arrests cell cycle of ovarian cancer, and restrains angiogenesis by modulating enhancer of zeste homolog 2 (EZH2) expression.

Downregulation of cell division cycle-associated protein 7 (CDCA7) suppresses cell proliferation, arrests cell cycle of ovarian cancer, and restrains angiogenesis by modulating enhancer of zeste homolog 2 (EZH2) expression.
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DOI:
10.1080/21655979.2021.1965441
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发表时间:
2021-12
期刊:
影响因子:
4.9
通讯作者:
Zhang Y
Zhang Y
中科院分区:
生物学2区
文献类型:
--
作者:
Cai C;Peng X;Zhang Y

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本研究旨在探讨细胞分裂周期相关蛋白7(CDCA 7)在卵巢癌(OC)发生发展中的生物学作用,并分析CDCA 7对OC细胞过程和血管生成的分子机制。OC组织和邻近正常组织中的CDCA 7表达从基因表达谱交互分析(GEPIA)获得,并且各种癌细胞系中的CDCA 7表达从癌细胞系百科全书(CCLE)获得。此外,通过Western blot分析和逆转录-定量聚合酶链反应(RT-qPCR)进一步证实了OC患者的癌旁正常组织和肿瘤组织以及正常卵巢上皮细胞(NOEC)和卵巢癌细胞(OVCAR 3、SKOV 3、CAOV-3、A2780)中的CDCA 7表达。同时采用免疫组化(IHC)法检测OC组织中CDCA 7的表达。然后,将shRNA-CDCA 7导入SKOV 3细胞进行功能实验。GeneMANIA数据库分析和免疫共沉淀(Co-IP)分析验证了CDCA 7与zeste增强子同源物2(EZH 2)之间的相互作用,以探索潜在的机制。CDCA 7在OC患者肿瘤组织和OC细胞系中表达升高。CDCA 7基因沉默抑制OC细胞的增殖、迁移和侵袭能力,并阻滞细胞周期。此外,CDCA 7敲低诱导HUVECs的体外血管生成较弱。在机制上,CDCA 7与EZH 2相互作用。下调CDCA 7通过抑制EZH 2表达来阻止血管生成。综上所述,本研究揭示了CDCA 7对OC细胞过程的影响和潜在机制,为OC治疗开发了一个有前途的分子靶点。
The purpose of the current study was to investigate the biological function of cell division cycle-associated protein 7 (CDCA7) on ovarian cancer (OC) progression and analyze the molecular mechanism of CDCA7 on OC cellular processes and angiogenesis. CDCA7 expression in OC tissues and adjacent normal tissues was obtained from Gene Expression Profiling Interactive Analysis (GEPIA) and in various cancer cell lines was obtained from Cancer Cell Line Encyclopedia (CCLE). Moreover, CDCA7 expression in adjacent normal tissues and tumor tissues of OC patients as well as in normal ovarian epithelial cells (NOEC) and ovarian cancer cells (OVCAR3, SKOV3, CAOV-3, A2780) was further confirmed via Western blot assay and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, Immunohistochemistry (IHC) was also applied for determination of CDCA7 expression in tissues of OC patients. Then, SKOV3 cells were introduced with shRNA-CDCA7 for functional experiments. GeneMANIA database analysis and coimmunoprecipitation (Co-IP) assay verified the interaction between CDCA7 and enhancer of zeste homolog 2 (EZH2) to probe the potential mechanism. CDCA7 expression was elevated in tumor tissues of OC patients and OC cell lines. CDCA7 silencing restrained the proliferative, migrative and invasive capacities and arrested cell cycle of OC cells. In addition, CDCA7 knockdown induced a weaker in vitro angiogenesis of HUVECs. Mechanistically, CDCA7 interacted with EZH2. Downregulation of CDCA7 arrested angiogenesis by suppressing EZH2 expression. To sum up, the current study revealed the impact and potential mechanism of CDCA7 on OC cellular processes, developing a promising molecular target for OC therapies.
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