ZNF750 exerted its Antitumor Action in Oral Squamous Cell Carcinoma by regulating E2F2.
ZNF750 exerted its Antitumor Action in Oral Squamous Cell Carcinoma by regulating E2F2.
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ZNF750通过调节E2F2发挥抗口腔鳞癌作用
DOI：
10.7150/jca.63919
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发表时间：
2021
影响因子：
3.9
通讯作者：
Chen HY
中科院分区：
文献类型：
--
作者：
Yang HL;Xu C;Yang YK;Tang WQ;Hong M;Pan L;Chen HY
细胞周期激活因子E2 F转录因子2（E2 F2）在肿瘤的发生、发展和转移中起着重要作用。先前的RNA序列分析（GSE 134835）显示，在口腔鳞状细胞癌（OSCC）中，锌指蛋白750（ZNF 750）显著降低了E2 F2。本研究的目的是确定E2 F2参与ZNF 750的抗肿瘤作用。通过皮下注射稳定的细胞系CAL-27 oeZNF 750或CAL-27 shZNF 750建立裸鼠异种移植模型。测量异种移植肿瘤体积和肿瘤重量。在体内和体外研究E2 F2、转录抑制因子如zeste增强子2（Ezh 2）、PHD指蛋白19（PHF 19）以及与细胞增殖或转移相关的基因的表达。荧光素酶法检测ZNF 750对E2 F2荧光素酶活性的调节作用。用E2 F2慢病毒共转导ZNF 750，研究E2 F2在ZNF 750抗肿瘤作用中的作用。ZNF 750可以抑制肿瘤的生长和转移，表现为肿瘤大小、肿瘤重量以及与细胞增殖和转移相关的基因减少。然而，所有这些都被ZNF 750基因的敲除逆转。此外，E2 F2荧光素酶活性被ZNF 750抑制。E2 F2可部分阻断ZNF 750的抗肿瘤作用，表现为ZNF 750 + E2 F2组的自我更新、侵袭、迁移能力增强，Ezh 2和MMP 13蛋白表达增加。然而，沉默E2 F2进一步增强ZNF 750的抗肿瘤作用。ZNF 750通过抑制E2 F2的活性，调节转录抑制因子，从而抑制OSCC的生长和转移。
Cell cycle activator E2F transcription factor 2 (E2F2) play a key role in tumor development and metastasis. Previous RNA sequence analysis (GSE134835) revealed E2F2 was significantly reduced by Zinc-finger protein 750 (ZNF750) in oral squamous cell carcinoma (OSCC). This study was aimed to determine the involvement of E2F2 in antitumor action of ZNF750. The nude mouse xenograft model was established by subcutaneously injection of stable cell line CAL-27oeZNF750 or CAL-27shZNF750. Xenograft tumor volume and tumor weight was measured. The expression of E2F2, transcriptional repressors such as enhancer of zeste 2 (Ezh2), PHD finger protein 19 (PHF19), and the genes related to cell proliferation or metastasis was studied in vivo or in vitro. Luciferase assay was performed to investigate regulation effect of ZNF750 on E2F2 luciferase activity. The involvement of E2F2 in the antitumor action of ZNF750 was studied by cotransduced ZNF750 with E2F2 lentivirus. The tumor growth and metastasis was repressed by ZNF750 manifested by reduced tumor size, tumor weight and the genes related to cell proliferation and metastasis. However, all of these were reversed by knockdown of the ZNF750 gene. Furthermore, E2F2 luciferase activity was inhibited by ZNF750. E2F2 partly blocked the antitumor action of ZNF750 manifested by increased self-renewal, invasion, migration, elevated Ezh2 and MMP13 protein expression in ZNF750 + E2F2 groups. However, silenced E2F2 further enhanced the antitumor action of ZNF750. ZNF750 depressed E2F2 activity and played a critical role in regulating transcriptional repressors for inhibiting the OSCC growth and metastasis in OSCC.