Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom.
J Immunol. 2013 Dec 15;191(12):6250-60. doi: 10.4049/jimmunol.1301728. Epub 2013 Nov 13.
Recent research has indicated a new mode of intercellular communication facilitated by the movement of RNA between cells. There is evidence that RNA can transfer between cells in a multitude of ways, including in complex with proteins or lipids or in vesicles, including apoptotic bodies and exosomes. However, there remains little understanding of the function of nucleic acid transfer between human cells. In this article, we report that human macrophages transfer microRNAs (miRNAs) to hepato-carcinoma cells (HCCs) in a manner that required intercellular contact and involved gap junctions. Two specific miRNAs transferred efficiently between these cells--miR-142 and miR-223--and both were endogenously expressed in macrophages and not in HCCs. Transfer of these miRNAs influenced posttranscriptional regulation of proteins in HCCs, including decreased expression of reporter proteins and endogenously expressed stathmin-1 and insulin-like growth factor-1 receptor. Importantly, transfer of miRNAs from macrophages functionally inhibited proliferation of these cancerous cells. Thus, these data led us to propose that intercellular transfer of miRNA from immune cells could serve as a new defense against unwanted cell proliferation or tumor growth.
最近的研究表明，RNA 在细胞间的运动为细胞间的通讯提供了一种新的模式。有证据表明，RNA 可以通过多种方式在细胞间转移，包括与蛋白质或脂质形成复合物，或通过包含凋亡小体和外泌体的囊泡。然而，人们对人类细胞间核酸转移的功能仍知之甚少。在本文中，我们报告称，人类巨噬细胞以需要细胞间接触并涉及间隙连接的方式将 microRNAs（miRNAs）转移到肝癌细胞（HCCs）中。这两种特定的 miRNA 在这些细胞之间有效地转移 - miR-142 和 miR-223 - 并且都在内源性地表达于巨噬细胞中而不是 HCC 中。这些 miRNA 的转移影响了 HCC 中蛋白质的转录后调节，包括报告蛋白和内源性表达的 stathmin-1 和胰岛素样生长因子-1 受体的表达减少。重要的是，从巨噬细胞转移 miRNA 可抑制这些癌细胞的增殖。因此，这些数据使我们提出，免疫细胞间的 miRNA 转移可以作为一种新的防御机制，防止不必要的细胞增殖或肿瘤生长。
