Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types.
Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types.
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DOI：
10.1186/1471-2164-13-357
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发表时间：
2012-08-01
期刊：
影响因子：
4.4
通讯作者：
Simpson DA
中科院分区：
文献类型：
--
作者：
Guduric-Fuchs J;O'Connor A;Camp B;O'Neill CL;Medina RJ;Simpson DA
microRNA（miRNA）是一类调节特定mRNA靶标表达的小RNA分子。它们可以从细胞中释放出来，通常封装在细胞外囊泡（EV）中，因此具有介导细胞间通信的潜力。已经提出，尽管该机制尚未确定，但某些miRNA可以选择性地出口。对电动汽车的miRNA含量的操纵对于将来的治疗应用非常重要。因此，我们希望评估哪些内源性miRNA富含电动汽车以及如何有效地表达miRNA。
通过深层测序分析了从HEK293T细胞和囊泡转染之前或之后的HEK293T细胞和囊泡的小RNA文库。发现一个miRNA的子集富含电动汽车。对其预测靶基因的途径分析表明在调节内吞作用中具有潜在的作用。其他细胞类型中的RT-QPCR和对公开数据的分析表明，这些miRNA中的许多往往会被广泛优先导出。尽管过表达的miR-146a在转染的细胞及其EV中都高度富集，但内源性miRNA的EV比没有严重改变。在许多不同的细胞类型中，miR-451始终是最高出口的miRNA。有趣的是，miR-451成熟需要Argonaute2（AGO2），并且已经证明AGO2中的敲除可以降低其他优先导出的miRNA的表达（例如miR-150和miR-142-3p）。
深度测序提供的全局表达数据证实，特定的miRNA富含HEK293T细胞释放的电动汽车。在一系列细胞类型中观察类似模式表明，可能存在选择性miRNA输出的常见机制。
MicroRNAs (miRNAs) are a class of small RNA molecules that regulate expression of specific mRNA targets. They can be released from cells, often encapsulated within extracellular vesicles (EVs), and therefore have the potential to mediate intercellular communication. It has been suggested that certain miRNAs may be selectively exported, although the mechanism has yet to be identified. Manipulation of the miRNA content of EVs will be important for future therapeutic applications. We therefore wished to assess which endogenous miRNAs are enriched in EVs and how effectively an overexpressed miRNA would be exported. Small RNA libraries from HEK293T cells and vesicles before or after transfection with a vector for miR-146a overexpression were analysed by deep sequencing. A subset of miRNAs was found to be enriched in EVs; pathway analysis of their predicted target genes suggests a potential role in regulation of endocytosis. RT-qPCR in additional cell types and analysis of publicly available data revealed that many of these miRNAs tend to be widely preferentially exported. Whilst overexpressed miR-146a was highly enriched both in transfected cells and their EVs, the cellular:EV ratios of endogenous miRNAs were not grossly altered. MiR-451 was consistently the most highly exported miRNA in many different cell types. Intriguingly, Argonaute2 (Ago2) is required for miR-451 maturation and knock out of Ago2 has been shown to decrease expression of other preferentially exported miRNAs (eg miR-150 and miR-142-3p). The global expression data provided by deep sequencing confirms that specific miRNAs are enriched in EVs released by HEK293T cells. Observation of similar patterns in a range of cell types suggests that a common mechanism for selective miRNA export may exist.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
64.5
作者：
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通讯作者：
Tuschl T
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni