IFN-γ induces epithelial-to-mesenchymal transition of cancer cells via an unique microRNA processing
Year: 2018
Type: preprint
Abstract: ABSTRACT Interferon-γ (IFNγ) is a potent cytokine in modulating tumor immunity and tumoricidal effects. We demonstrate a new function of IFNγ in inducing epithelial-to-mesenchymal transition (EMT) in normal and cancer cells from different cell types. IFNγ activates JAK-STAT signaling pathway leading to the transcription of IFN-stimulated genes (ISGs), such as interferon-induced tetratricopeptide repeat 5 (IFIT5). We unveil a new function of IFIT5 complex in degrading precursor microRNAs (pre-miRNA) that include pre-miR-363 from the miR-106a-363 cluster, as well as pre-miR-101 and pre-miR-128 with a similar 5’-end structure with pre-miR-363. Noticeably, these suppressive miRNAs have similar functions by targeting EMT transcription factors in prostate cancer (PCa) cells. We further demonstrated that IFIT5 plays a critical role in IFNγ-induced cell invasiveness in vitro and lung metastasis in vivo . Clinically, IFIT5 is highly elevated in high-grade PCa and its expression inversely correlates with these suppressive miRNAs. Altogether, this study unveils pro-tumorigenic role of the IFN pathway via a new mechanism of action, which certainly raises concern about its clinical application.
DOI: 10.1101/355263
Institutions: The University of Texas Southwestern Medical Center, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, The University of Texas at Arlington, Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, National Research Council, NYU Langone Health, Chang Gung University, National Chung Hsing University, China Medical University, China Medical University Hospital
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2809939804