Interferon-induced IFIT5 promotes epithelial-to-mesenchymal transition leading to renal cancer invasion

American Journal of Clinical and Experimental Urology

Junhang Luo¹  Hsin-Chih Yeh²  Jiming Bao³  Junjie Cen⁴  U-Ging Lo⁵ 

[1] Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China;Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Taiwan, Republic of China;Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Republic of China;Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Republic of China;Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

关键词: Interferon (IFN);    interferon-induced tetratricopeptide repeat 5 (IFIT5);    epithelial-to-mesenchymal transition (EMT);   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Interferon is known as a pleiotropic factor in innate immunity, cancer immunity and therapy. Despite an objective short-term response of interferon (IFN) therapy in renal cell carcinoma (RCC) patients, the potential adverse effect of IFN on RCC cells is not fully understood. In this study, we demonstrate that IFNs can enhance RCC invasion via a new mechanism of IFIT5-mediated tumor suppressor microRNA (miRNA) degradation resulted in the elevation of Slug and ZEB1 and epithelial-to-mesenchymal transition (EMT). Clinically, a significant upregulation of IFNγ signaling pathway (such as IFNGR1, IFNGR2, STAT1 and STAT2) is observed in RCC patients with metastatic disease. Overall, this study provides a new mechanism of action of IFN-elicited canonical pathway in regulating suppressor miRNAs. Most importantly, it highlights the potential pro-metastatic effect of IFNs, which could undermine the clinical applicability of IFNs for treating RCC patients.

【 授权许可】

CC BY-NC