miR-139 通过与 RIG-1 结合诱导前列腺癌细胞产生干扰素-β反应。
MiR-139 Induces an Interferon-β Response in Prostate Cancer Cells by Binding to RIG-1.
机构信息
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.
出版信息
Cancer Genomics Proteomics. 2021 May-Jun;18(3):197-206. doi: 10.21873/cgp.20252.
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.
摘要
背景
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。
材料和方法
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。
结果
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。
结论
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。
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