Department of Urology, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, Jiangsu Province, China.
Department of Urology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China.
Nutr Cancer. 2020;72(7):1115-1124. doi: 10.1080/01635581.2019.1675721. Epub 2019 Nov 24.
TRIM13, a member of the TRIM family, is a RING domain containing E3 ubiquitin ligase which plays critical roles in diverse cellular processes including cell death, cancer and antiviral immunity. However, its expression and molecular mechanism on renal cell carcinoma (RCC) have not been characterized. This study explored the clinical significance and biological function of TRIM13 in human RCC. Western blot analyses and Immunohistochemical were performed in RCC tissues. The clinical relevance of TRIM13 in RCC was evaluated by immunohistochemical staining using tissue microarray. The role of TRIM13 in migration was studied in renal cell carcinoma cell lines of 786- through knocking down TRIM13 with siRNA and over-expression of TRIM13. The regulation of TRIM13 on migration and invasion were determined by wound-healing and transwell assays. Western blot analyses showed that TRIM13 expression was dramatically decreased in RCC tissues compared with adjacent non-tumorous tissues. Up-regulation of TRIM13 in 786- cells resulted in decreased NF-kB, MMP-9 and p-AKT levels and the capability for migration and invasion. In contrast, the ectopic expression of TRIM13 decreased the migration and invasion ability of 786-O cells. These findings indicate that TRIM13 decreases RCC metastasis and invasion may serve as a candidate RCC prognostic marker and a potential therapeutic target.
TRIM13 是 TRIM 家族的一员,是一种含有 RING 结构域的 E3 泛素连接酶,在多种细胞过程中发挥关键作用,包括细胞死亡、癌症和抗病毒免疫。然而,其在肾细胞癌(RCC)中的表达和分子机制尚未得到描述。本研究探讨了 TRIM13 在人 RCC 中的临床意义和生物学功能。在 RCC 组织中进行了 Western blot 分析和免疫组织化学分析。通过组织微阵列进行免疫组织化学染色评估 TRIM13 在 RCC 中的临床相关性。通过 siRNA 敲低 TRIM13 和过表达 TRIM13 研究了 TRIM13 在肾癌细胞系 786-O 中的迁移作用。通过划痕愈合和 Transwell 测定确定了 TRIM13 对迁移和侵袭的调节作用。Western blot 分析显示,与相邻非肿瘤组织相比,RCC 组织中 TRIM13 的表达明显降低。在 786-O 细胞中上调 TRIM13 导致 NF-κB、MMP-9 和 p-AKT 水平降低以及迁移和侵袭能力降低。相比之下,TRIM13 的异位表达降低了 786-O 细胞的迁移和侵袭能力。这些发现表明,TRIM13 降低了 RCC 的转移和侵袭,可能作为 RCC 预后标志物和潜在的治疗靶点。