IFNγ-Induced IFIT5 Promotes Epithelial-to-Mesenchymal Transition in Prostate Cancer via miRNA Processing
Abstract
IFNγ, 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 IFNγ 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′-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 IFNγ-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 prometastatic role of the IFNγ pathway via a new mechanism of action, which raises concerns about its clinical application.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 15, 2019
- Source ID
- 10.1158/0008-5472.can-18-2207
Entities
People
- Andrew Dang
- Arnaldo A. Arbini
- Chih-ho Lai
- Dalin He
- Diane Yang
- Elizabeth Hernandez
- Ganesh V Raj
- Ho Lin
- Jer-Tsong Hsieh
- John Santoyo
- Leah Gandee
- Loredana Moro
- Payal Kapur
- Rajni Sonavane
- Rey-chen Pong
- Shihong Ma
- Shu-fen Tseng
- Tony Jun Huang
- U-ging Lo
Organizations
- Chang Gung University
- Kaohsiung Medical University
- NYU Langone Health
- National Chung Hsing University
- National Institutes of Health
- National Science and Technology Council
- United States Army
- University of Texas at Arlington
- University of Texas at Austin
- Xi'an Jiaotong University