@article{7b8b4ed8cba1403ba2995cd8adefd474,
title = "IFNG-induced IFIT5 promotes epithelial-to-mesenchymal transition in prostate cancer via miRNA processing",
abstract = " IFNg, a potent cytokine known to modulate tumor immunity and tumoricidal effects, is highly elevated in patients with prostate cancer after radiation. In this study, we demonstrate that IFNg can induce epithelial-to-mesenchymal transition (EMT) in prostate cancer cells via the JAK–STAT signaling pathway, leading to the transcription of IFN-stimulated genes (ISG) such as IFN-induced tetratricopeptide repeat 5 (IFIT5). We unveil a new function of IFIT5 complex in degrading precursor miRNAs (pre-miRNA) that includes pre-miR-363 from the miR-106a-363 cluster as well as pre-miR-101 and pre-miR-128, who share a similar 5 0 -end structure with pre-miR-363. These suppressive miRNAs exerted a similar function by targeting EMT transcription factors in prostate cancer cells. Depletion of IFIT5 decreased IFNg-induced cell invasiveness in vitro and lung metastasis in vivo. IFIT5 was highly elevated in high-grade prostate cancer and its expression inversely correlated with these suppressive miRNAs. Altogether, this study unveils a pro-metastatic role of the IFNg pathway via a new mechanism of action, which raises concerns about its clinical application.",
author = "Lo, {U. Ging} and Pong, {Rey Chen} and Diane Yang and Leah Gandee and Elizabeth Hernandez and Andrew Dang and Lin, {Chung Jung} and John Santoyo and Shihong Ma and Rajni Sonavane and Jun Huang and Tseng, {Shu Fen} and Loredana Moro and Arbini, {Arnaldo A.} and Payal Kapur and Raj, {Ganesh V.} and Dalin He and Lai, {Chih Ho} and Ho Lin and Hsieh, {Jer Tsong}",
note = "Funding Information: We thank Dr. Collins (University of California, Berkeley, CA) for providing IFIT5 cDNA constructs, Dr. Dong (Emory University, Atlanta, GA) for providing the psiCHECK2-Slug3′UTR plasmid. Drs. Kou-Juey Wu (China Medical University, Taichung, Taiwan) and Dr. Vimal Selvaraj (Cornell University, Ithaca, NY) for the helpful discussion. We also acknowledge the assistance of the Southwestern Small Animal Imaging Resource, which is supported in part by the Harold C. Simmons Cancer Center through an NCI Cancer Center Support Grant (1P30 CA142543), and the Department of Radiology (NIH 1S10RR024757). This work was supported by grants from the United States Army (W81XWH-11-1-0491 and W81XWH-16-1-0474 to J.-T. Hsieh) and Funding Information: We thank Dr. Collins (University of California, Berkeley, CA) for providing IFIT5 cDNA constructs, Dr. Dong (Emory University, Atlanta, GA) for providing the psiCHECK2-Slug30UTR plasmid. Drs. Kou-Juey Wu (China Medical University, Taichung, Taiwan) and Dr. Vimal Selvaraj (Cornell University, Ithaca, NY) for the helpful discussion. We also acknowledge the assistance of the Southwestern Small Animal Imaging Resource, which is supported in part by the Harold C. Simmons Cancer Center through an NCI Cancer Center Support Grant (1P30 CA142543), and the Department of Radiology (NIH 1S10RR024757). This work was supported by grants from the United States Army (W81XWH-11-1-0491 and W81XWH-16-1-0474 to J.-T. Hsieh) and (W81XWH-14-1-0249 to U.-G. Lo), and the Ministry of Science and Technology in Taiwan (MOST103-2911-I-005-507 to H. Lin). Publisher Copyright: {\textcopyright} 2018 American Association for Cancer Research.",
year = "2019",
doi = "10.1158/0008-5472.CAN-18-2207",
language = "English (US)",
volume = "79",
pages = "1098--1112",
journal = "Cancer research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "6",
}