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

  • Exp Cell Res. 2021 Oct 1;407(1):112799. doi: 10.1016/j.yexcr.2021.112799.
Ding Wang  1 ,  Xiaodong Wei  1 ,  Xuyang Chen  1 ,  Qian Wang  1 ,  Jinghua Zhang  1 ,  Dhan V Kalvakolanu  2 ,  Baofeng Guo  3 ,  Ling Zhang  4
Affiliations
  • 1. Key Laboratory of Pathobiology, Ministry of Education, And Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, PR China.
  • 2. Greenebaum NCI Comprehensive Cancer Center, Department of Microbiology and Immunology University of Maryland School Medicine, Baltimore, MD, USA.
  • 3. Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun, PR China. Electronic address: [email protected].
  • 4. Key Laboratory of Pathobiology, Ministry of Education, And Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, PR China. Electronic address: [email protected].
PMID: 34461110 DOI: 10.1016/j.yexcr.2021.112799
Abstract

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.

Keywords
CRC; GRIM-19; MDM2; SIRT7; p53.
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