The dual role of TRIM3 in colorectal cancer dependent on p53 status by retaining p53 in the cytoplasm to decrease its expression in the nuclei

Abstract

Abstract Colorectal cancer is a very heterogeneous disease caused by the interaction of genetic and environmental factors. P53, a few exceptions, is a frequent mutation and plays a critical role in the adenoma-carcinoma transition during the tumorous pathological process. Our team screened the series of genes’ expression by high-content screening techniques to discover TRIM3 a newly tumor-associated gene in CRC. TRIM3 demonstrated both tumor-suppressive and tumorigenic features dependent on p53 wild or mutant status in cell experiments in our study. TRIM3 could directly interact with the C terminus of p53 (residues 320 to 393), a common segment of wtp53 and mutp53. Moreover, TRIM3 could decrease p53 levels in the nuclei by retaining them in the cytoplasm to exert different neoplastic biological features in a wtp53 or mutp53 dependent pathway. Chemotherapy resistance develops in nearly all patients with advanced CRC and seriously limits the therapeutic efficacies of anticancer drugs. TRIM3 could successfully reverse the chemotherapy resistance of oxaliplatin in mutp53 CRC cells by decreasing mutp53 in the nuclei to downregulate the multidrug resistance gene. Therefore, TRIM3 could be a potential therapeutic strategy to improve the survival of CRC patients with mutp53 by degradation mutp53 in the nuclei.