Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China.
Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China.
Oncol Rep. 2018 Sep;40(3):1251-1260. doi: 10.3892/or.2018.6525. Epub 2018 Jun 26.
TRIM58 is a member of the tripartite motif protein (TRIM) family of E3 ubiquitin ligases. Aberrant gene methylation of TRIM58 has been reported in liver and lung cancer and indicates a poor patient prognosis. However, the expression level and functional role of TRIM58 in colorectal cancer (CRC) have yet to be elucidated. In the present study, we found that TRIM58 expression was significantly suppressed in human CRC and was inversely correlated with CRC progression. Additionally, overall survival was significantly reduced in patients with low TRIM58 expression in CRC tumors. In vitro studies demonstrated that ectopic TRIM58 overexpression strongly inhibited CRC cell invasion but had minimal effects on cell proliferation, colonization and migration. Furthermore, TRIM58 suppression enhanced the expression of epithelial-to-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) genes. Thus, our findings suggest that TRIM58 is a potential prognostic marker of CRC and functions as a tumor-suppressor gene via inhibition of cancer cell invasion through EMT and MMP activation.
TRIM58 是三部分基序蛋白 (TRIM) 家族的 E3 泛素连接酶的成员。TRIM58 基因的异常甲基化已在肝癌和肺癌中报道,并表明患者预后不良。然而,TRIM58 在结直肠癌 (CRC) 中的表达水平和功能作用尚待阐明。在本研究中,我们发现 TRIM58 在人 CRC 中的表达显著受抑制,且与 CRC 进展呈负相关。此外,CRC 肿瘤中 TRIM58 低表达的患者总生存率显著降低。体外研究表明,异位 TRIM58 过表达强烈抑制 CRC 细胞侵袭,但对细胞增殖、定植和迁移的影响最小。此外,TRIM58 抑制增强了上皮间质转化 (EMT) 和基质金属蛋白酶 (MMP) 基因的表达。因此,我们的研究结果表明,TRIM58 是 CRC 的潜在预后标志物,通过 EMT 和 MMP 激活抑制癌细胞侵袭来发挥肿瘤抑制基因的功能。