MiR-139 Induces an Interferon-β Response in Prostate Cancer Cells by Binding to RIG-1
Robert K. Nam, Tania Benatar, Yutaka Amemiya, Arun Seth
Abstract
BACKGROUND: We previously identified a panel of five miRNAs associated with prostate cancer recurrence and metastasis. Expression of one of the down-regulated miRNAs, miR-139-5p, was significantly associated with a lower incidence of biochemical recurrence and metastasis. Transcriptome profiling of miR-139-expressing prostate cancer cells revealed up-regulation of genes involved in interferon (IFN) stimulation. The association between miR-139 and IFN-β was further explored in this study. MATERIALS AND METHODS: We examined miR-139 transfected PC3, Du145 and LNCaP cells and the associated IFN response by transcriptome sequencing, immunoblotting and pulldown assays. RESULTS: Treatment of prostate cancer cells by miR-139 resulted in the up-regulation of IFN-related genes. Specifically, miR-139 induced expression of the IFN-β protein. The ability of miR-139 to induce IFN-β was due to its binding to RIG-1 and the induction of IFN-related genes was found to be dependent on RIG-1 expression. CONCLUSION: miR-139 acts as an immune agonist of RIG-1 to enhance IFN-β response in prostate cancer cells.