Department of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Platform Biological Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
Cancer Genomics Proteomics. 2021 May-Jun;18(3):197-206. doi: 10.21873/cgp.20252.
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.
We examined miR-139 transfected PC3, Du145 and LNCaP cells and the associated IFN response by transcriptome sequencing, immunoblotting and pulldown assays.
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.
miR-139 acts as an immune agonist of RIG-1 to enhance IFN-β response in prostate cancer cells.
我们之前确定了一组与前列腺癌复发和转移相关的五个 miRNAs。下调的 miRNAs 之一 miR-139-5p 的表达与生化复发和转移的发生率降低显著相关。miR-139 表达的前列腺癌细胞的转录组分析显示，干扰素 (IFN) 刺激相关基因上调。本研究进一步探讨了 miR-139 与 IFN-β 之间的关联。
我们通过转录组测序、免疫印迹和下拉实验检测了转染 miR-139 的 PC3、Du145 和 LNCaP 细胞以及相关的 IFN 反应。
miR-139 处理前列腺癌细胞导致 IFN 相关基因上调。具体而言，miR-139 诱导 IFN-β 蛋白的表达。miR-139 诱导 IFN-β 的能力归因于其与 RIG-1 的结合，并且发现 IFN 相关基因的诱导依赖于 RIG-1 的表达。
miR-139 作为 RIG-1 的免疫激动剂，增强前列腺癌细胞中的 IFN-β 反应。
