MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response
MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response
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DOI：
10.1073/pnas.1209414109
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发表时间：
2012-07-31
影响因子：
11.1
通讯作者：
Croce, Carlo M.
中科院分区：
文献类型：
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作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
microRNA（miRNAs）是一种长度为19-24个核苷酸的小的非编码RNA，其调节基因表达，并且在大多数类型的癌症中异常表达。在癌症患者的血液中也检测到了miRNAs，它们可以作为循环生物标志物。已经表明，外泌体内分泌的miRNA可以从细胞转移到细胞，并且可以通过与其靶信使RNA的典型结合来调节接收细胞中的基因表达。在这里，我们发现肿瘤分泌的miR-21和miR-29 a也可以通过另一种机制发挥作用，通过在免疫细胞中作为配体与Toll样受体（TLR）家族的受体（鼠TLR 7和人TLR 8）结合，引发TLR介导的促转移炎症反应，最终可能导致肿瘤生长和转移。因此，通过充当TLR的旁分泌激动剂，分泌的miRNA是肿瘤微环境的关键调节剂。miRNA的这种作用机制涉及肿瘤-免疫系统通信，并且在肿瘤生长和扩散中很重要，因此代表了癌症治疗的可能靶点。
MicroRNAs (miRNAs) are small noncoding RNAs, 19-24 nucleotides in length, that regulate gene expression and are expressed aberrantly in most types of cancer. MiRNAs also have been detected in the blood of cancer patients and can serve as circulating biomarkers. It has been shown that secreted miRNAs within exosomes can be transferred from cell to cell and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs. Here we show that tumor-secreted miR-21 and miR-29a also can function by another mechanism, by binding as ligands to receptors of the Toll-like receptor (TLR) family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response that ultimately may lead to tumor growth and metastasis. Thus, by acting as paracrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is implicated in tumor-immune system communication and is important in tumor growth and spread, thus representing a possible target for cancer treatment.