IFNG-induced IFIT5 promotes epithelial-to-mesenchymal transition in prostate cancer via miRNA processing

U. Ging Lo, Rey Chen Pong, Diane Yang, Leah Gandee, Elizabeth Hernandez, Andrew Dang, Chung Jung Lin, John Santoyo, Shihong Ma, Rajni Sonavane, Jun Huang, Shu Fen Tseng, Loredana Moro, Arnaldo A. Arbini, Payal Kapur, Ganesh V. Raj, Dalin He, Chih Ho Lai, Ho Lin, Jer Tsong Hsieh

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1098-1112
Number of pages15
JournalCancer research
Volume79
Issue number6
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Lo, U. G., Pong, R. C., Yang, D., Gandee, L., Hernandez, E., Dang, A., Lin, C. J., Santoyo, J., Ma, S., Sonavane, R., Huang, J., Tseng, S. F., Moro, L., Arbini, A. A., Kapur, P., Raj, G. V., He, D., Lai, C. H., Lin, H., & Hsieh, J. T. (2019). IFNG-induced IFIT5 promotes epithelial-to-mesenchymal transition in prostate cancer via miRNA processing. Cancer research, 79(6), 1098-1112. https://doi.org/10.1158/0008-5472.CAN-18-2207