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TRIM28 通过 mTOR 信号通路促进宫颈癌生长。

TRIM28 promotes cervical cancer growth through the mTOR signaling pathway.

机构信息

Department of Gynaecology and Obstetrics, Shanghai Eighth People's Hospital Affiliated to Jiangsu University, Shanghai 200235, P.R. China.

出版信息

Oncol Rep. 2018 Apr;39(4):1860-1866. doi: 10.3892/or.2018.6235. Epub 2018 Jan 26.

DOI:10.3892/or.2018.6235
PMID:29393469
Abstract

Aberrant expression of tripartite motif-containing protein 28 (TRIM28) has been demonstrated in several human cancers; however, its biological function and related mechanism in cervical cancer remain unclear. In this study, we compared TRIM28 expression between cervical cancer and adjacent normal tissues, and detected significant elevation in TRIM28 expression levels in the cervical cancer tissues. Moreover, TRIM28 overexpression promoted the proliferation, colony formation, and cell cycle progression of cervical cancer cell lines, as well as the growth of xenograft tumors in nude mice, whereas knockdown of TRIM28 had the opposite effects. Evaluation of the potential mechanism demonstrated that TRIM28 promoted cervical cancer cell growth by activating the mammalian target of rapamycin (mTOR) signaling pathway. In support of this finding, TRIM28-induced cell proliferation was abolished by treatment with everolimus, a specific mTOR inhibitor. These results suggest that TRIM28 plays a pivotal role in cervical cancer cell proliferation and might serve as a potential therapeutic target.

摘要

三结构域蛋白 28(TRIM28)的异常表达已在多种人类癌症中得到证实;然而,其在宫颈癌中的生物学功能和相关机制尚不清楚。在这项研究中,我们比较了宫颈癌和相邻正常组织中 TRIM28 的表达水平,发现 TRIM28 在宫颈癌组织中的表达水平显著升高。此外,TRIM28 的过表达促进了宫颈癌细胞系的增殖、集落形成和细胞周期进程,以及裸鼠异种移植肿瘤的生长,而 TRIM28 的敲低则产生相反的效果。对潜在机制的评估表明,TRIM28 通过激活哺乳动物雷帕霉素靶蛋白(mTOR)信号通路促进宫颈癌细胞的生长。支持这一发现的是,特异性 mTOR 抑制剂依维莫司可消除 TRIM28 诱导的细胞增殖。这些结果表明,TRIM28 在宫颈癌细胞增殖中发挥着关键作用,可能成为一个有潜力的治疗靶点。

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Oncol Rep. 2018 Apr;39(4):1860-1866. doi: 10.3892/or.2018.6235. Epub 2018 Jan 26.
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