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Abstract
Abstract As a key tumor suppressor, p53 plays crucial roles in gastric cancer initiation and progression. However, the underlying mechanisms for the down-regulation of p53 in gastric cancer patients are not fully understood. Several tripartite motif (TRIM) family proteins are identified to be involved in the tumorigenesis of multiple cancer types, but the significance and biological function of a new TRIM family protein, TRIM59, in terms of whether and how it affects p53 signaling in gastric cancer are largely unknown. We analyzed multiple microarray datasets from the Oncomine database and tested the expression level of TRIM59 in gastric tumors vs. their matched normal tissues and in gastric carcinoma cell lines using quantitative-polymerase chain reactions (Q-PCR) and immunohistochemical staining. We found Expression of TRIM59 was significantly up-regulated in gastric cancer and strongly associated with poor prognosis. TRIM59 knockdown led to significantly attenuated gastric cancer cell proliferation, clone formation, migration, and in vivo xenograft tumorigenicity, whereas over-expression of TRIM59 showed the opposite effects. Mechanistically, TRIM59 interacted with p53 and enhanced ubiquitination and degradation of the p53 protein. In addition, elevated expression of TRIM59 correlated with down-regulation of p53 target genes in human gastric tumors. In summary, TRIM59 is a novel prognostic marker for gastric cancer and promotes tumorigenesis through facilitating p53 ubiquitination and degradation. Citation Format: Zhicheng Zhou, You Wang, Jian Li, Hui Cao, Helen He Zhu, Wei-Qiang Gao. TRIM59, a novel prognostic marker for gastric cancer, promotes tumorigenesis via ubiquitination and degradation of the p53 tumor suppressor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 473. doi:10.1158/1538-7445.AM2014-473
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