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MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation

机译:微小RNa从人巨噬细胞转移到肝癌细胞并抑制增殖

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摘要

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. Copyright © 2013 by The American Association of Immunologists, Inc.
机译:最近的研究表明,RNA在细胞之间的移动促进了细胞间通讯的新模式。有证据表明RNA可以多种方式在细胞之间转移,包括与蛋白质或脂质复合或在囊泡中(包括凋亡小体和外泌体)。然而,对人类细胞之间核酸转移功能的了解仍然很少。在本文中,我们报道了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microRNA(miRNA)转移至肝癌细胞(HCC)。两种特异性miRNA在这些细胞之间有效转移-miR-142和miR-223-两者均在巨噬细胞而不是HCC中内源表达。这些miRNA的转移影响了HCC中蛋白质的转录后调控,包括报告蛋白的表达降低以及内源性表达的stathmin-1和胰岛素样生长因子1受体。重要的是,从巨噬细胞转移miRNA功能上抑制了这些癌细胞的增殖。因此,这些数据使我们提出,miRNA从免疫细胞的细胞间转移可以作为对有害细胞增殖或肿瘤生长的新防御。美国免疫学家协会版权所有©2013。

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