GRIM-19 inhibits proliferation and induces apoptosis in a p53-dependent manner in colorectal cancer cells through the SIRT7/PCAF/MDM2 axis

被引：15
作者：
Wang, Ding [1 ,2 ]
Wei, Xiaodong [1 ,2 ]
Chen, Xuyang [1 ,2 ]
Wang, Qian [1 ,2 ]
Zhang, Jinghua [1 ,2 ]
Kalvakolanu, Dhan V. [3 ]
Guo, Baofeng [4 ]
Zhang, Ling [1 ,2 ]
机构：
[1] Jilin Univ, Key Lab Pathobiol, Minist Educ, Changchun, Peoples R China
[2] Jilin Univ, Dept Pathophysiol, Coll Basic Med Sci, Changchun, Peoples R China
[3] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Greenebaum NCI Comprehens Canc Ctr, Baltimore, MD 21201 USA
[4] Jilin Univ, Dept Plast Surg, China Japan Union Hosp, 126 Xiantai St, Changchun 130033, Jilin, Peoples R China
来源：
EXPERIMENTAL CELL RESEARCH | 2021年 / 407卷 / 01期
基金：
中国国家自然科学基金;
关键词：
GRIM-19; CRC; p53; MDM2; SIRT7; EXPRESSION; OVEREXPRESSION; METASTASIS; MECHANISMS; ROS;
D O I：
10.1016/j.yexcr.2021.112799
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Colorectal cancer (CRC) is the leading deadly cancer worldwide. Gene associated with retinoid-IFN-induced mortality-19 (GRIM-19), a novel tumor suppressor, has been reported to be expressed at low levels in human CRC. However, the role of GRIM-19 in CRC progression and the corresponding detailed mechanisms are unclear. The results of this study indicated that GRIM-19 expression is related to CRC progression. Overexpression of GRIM-19 was found to inhibit CRC cell proliferation and induce apoptosis in vitro and in vivo. Our results demonstrated that GRIM-19 suppresses CRC through posttranslational regulation of p53, in which SIRT7 is activated by GRIM-19 and triggers PCAF-mediated MDM2 ubiquitination, eventually stabilizing the p53 protein. We also observed that GRIM-19 enhances the effect of oxaliplatin against CRC. In conclusion, GRIM-19 plays an important role in CRC development and is a potential biomarker and therapeutic target for clinical treatment of CRC.
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页数：11
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