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USP7 promotes proliferation of papillary thyroid carcinoma cells through TBX3-mediated p57KIP2 repression.
Molecular and Cellular Endocrinology ( IF 3.8 ) Pub Date : 2020-09-20 , DOI: 10.1016/j.mce.2020.111037
Peiyi Xie 1 , Hui Wang 2 , Jing Xie 3 , Zhaoxia Huang 4 , Sha Chen 5 , Xiuzhi Cheng 5 , Xinyue Zhang 5 , Fanrong Liu 5 , Yun Li 6 , Da Huang 7
Affiliation  

Ubiquitin-specific protease 7 (USP7/HAUSP) is known to regulate multiple cellular phenomena, including cell cycle progression and proliferation, and is involved in binding and stabilizing specific target proteins through deubiquitylation. However, the detailed role of USP7 in papillary thyroid carcinoma (PTC) remains to be investigated. In this study, our results showed that USP7 was upregulated in PTC tissues compared with adjacent nontumour tissues. Consistently, a series of gain/loss functional assays in vivo and in vitro demonstrated the role of USP7 in promoting PTC cell proliferation. Furthermore, we showed that there was a negative correlation between USP7 and the CDK inhibitor p57KIP2 expression in PTC tissues and that USP7 facilitated PTC cell proliferation by inhibiting p57KIP2. Mechanistically, USP7 inhibited p57KIP2 expression by modulating TBX3, directly binding to TBX3, and decreasing its ubiquitination and degradation. Our findings demonstrated that USP7 played a critical oncogenic role in PTC tumorigenesis, suggesting that USP7 might act as a prognostic and therapeutic target for PTC progression.



中文翻译:

USP7通过TBX3介导的p57KIP2阻遏促进甲状腺乳头状癌细胞的增殖。

众所周知,泛素特异性蛋白酶7(USP7 / HAUSP)可调节多种细胞现象,包括细胞周期进程和增殖,并参与通过去泛素化作用结合和稳定特定靶蛋白的过程。但是,USP7在甲状腺乳头状癌(PTC)中的详细作用仍有待研究。在这项研究中,我们的结果表明,与邻近的非肿瘤组织相比,USP7在PTC组织中被上调。一致地,体内和体外的一系列增益/损失功能测定法证明了USP7在促进PTC细胞增殖中的作用。此外,我们表明USP7与CDK抑制剂p57 KIP2在PTC组织中的表达呈负相关,并且USP7通过抑制p57 KIP2促进了PTC细胞的增殖。。从机理上讲,USP7通过调节TBX3,直接结合TBX3并减少其泛素化和降解来抑制p57 KIP2表达。我们的研究结果表明,USP7在PTC肿瘤发生中起着至关重要的致癌作用,这表明USP7可能作为PTC进展的预后和治疗靶标。

更新日期:2020-09-26
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