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.

结直肠癌 (CRC) 是全球主要的致命癌症。据报道，与类视黄醇干扰素诱导的死亡率相关的基因 19 (GRIM-19)，一种新型肿瘤抑制因子，在人类 CRC 中以低水平表达。然而，GRIM-19 在 CRC 进展中的作用和相应的详细机制尚不清楚。本研究结果表明，GRIM-19 表达与 CRC 进展有关。GRIM-19 的过表达被发现在体外和体内抑制 CRC 细胞增殖并诱导细胞凋亡. 我们的结果表明，GRIM-19 通过 p53 的翻译后调节抑制 CRC，其中 SIRT7 被 GRIM-19 激活并触发 PCAF 介导的 MDM2 泛素化，最终稳定 p53 蛋白。我们还观察到 GRIM-19 增强了奥沙利铂对 CRC 的作用。总之，GRIM-19在结直肠癌的发生发展中发挥着重要作用，是结直肠癌临床治疗的潜在生物标志物和治疗靶点。