Li Rongkun, Zhu Lili, Peng Yangxizi, Zhang Xiaoxin, Dai Chunhua, Liu Dejun
Institute of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Oncol. 2021 Sep 9;11:695740. doi: 10.3389/fonc.2021.695740. eCollection 2021.
Emerging evidence suggests that the tripartite motif (TRIM) family play important roles in tumor development and progression. Tripartite motif-containing 50 (TRIM50) is a member of the TRIM family, but little is known regarding its expression and potential functional roles in cancer. In this study, we first analyzed the expression pattern and clinical significance of TRIM50 in pancreatic cancer and found that TRIM50 expression is significantly reduced in pancreatic cancer tissues and its downregulation is associated with poor survival for pancreatic cancer patients. Functionally, TRIM50 overexpression in pancreatic cancer cells decreases their proliferation and motility capabilities and reverses the epithelial-mesenchymal transition (EMT) process, whereas TRIM50 depletion had the opposite effects. Mechanically, TRIM50 directly interacts with Snail1, a key regulator of EMT, and acts as an E3 ubiquitin ligase to target Snail1 for ubiquitous degradation. The function of TRIM50 in suppressing cell migration and EMT depends on TRIM50-promoted Snail1 degradation. In conclusion, our findings identify TRIM50 as a tumor suppressor that inhibits pancreatic cancer progression and reverses EMT degrading Snail1 and provide new insights into the progression of pancreatic cancer.
新出现的证据表明，三联基序（TRIM）家族在肿瘤的发生和发展中起重要作用。含三联基序蛋白50（TRIM50）是TRIM家族的成员之一，但关于其在癌症中的表达及潜在功能作用却知之甚少。在本研究中，我们首先分析了TRIM50在胰腺癌中的表达模式及临床意义，发现TRIM50在胰腺癌组织中的表达显著降低，且其下调与胰腺癌患者的不良预后相关。在功能方面，胰腺癌细胞中TRIM50的过表达降低了它们的增殖和迁移能力，并逆转了上皮-间质转化（EMT）过程，而TRIM50的缺失则产生相反的效果。机制上，TRIM50直接与EMT的关键调节因子Snail1相互作用，并作为一种E3泛素连接酶，靶向Snail1进行泛素化降解。TRIM50在抑制细胞迁移和EMT中的功能依赖于TRIM50促进的Snail1降解。总之，我们的研究结果确定TRIM50是一种肿瘤抑制因子，它通过降解Snail1来抑制胰腺癌进展并逆转EMT，为胰腺癌的进展提供了新的见解。
