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

Autor: Wang D; Key Laboratory of Pathobiology, Ministry of Education, And Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, PR China., Wei X; Key Laboratory of Pathobiology, Ministry of Education, And Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, PR China., Chen X; Key Laboratory of Pathobiology, Ministry of Education, And Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, PR China., Wang Q; Key Laboratory of Pathobiology, Ministry of Education, And Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, PR China., Zhang J; Key Laboratory of Pathobiology, Ministry of Education, And Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, PR China., Kalvakolanu DV; Greenebaum NCI Comprehensive Cancer Center, Department of Microbiology and Immunology University of Maryland School Medicine, Baltimore, MD, USA., Guo B; Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun, PR China. Electronic address: gbf@jlu.edu.cn., Zhang L; Key Laboratory of Pathobiology, Ministry of Education, And Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, PR China. Electronic address: zhangling3@jlu.edu.cn.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2021 Oct 01; Vol. 407 (1), pp. 112799. Date of Electronic Publication: 2021 Aug 28.
DOI: 10.1016/j.yexcr.2021.112799
Abstrakt: 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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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