microRNA control of cell-cell signaling during development and disease
microRNA control of cell-cell signaling during development and disease
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DOI：
10.4161/cc.6447
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发表时间：
2008-08-01
期刊：
影响因子：
4.3
通讯作者：
Lai, Eric C.
中科院分区：
文献类型：
--
作者：
Hagen, Joshua W.;Lai, Eric C.
MicroRNAs(MiRNAs)是关键的转录后调控因子，可能共同控制大多数动物基因。随着数以千计的miRNAs的发现，一个紧迫的挑战是了解它们的特定生物活性。许多人预测miRNA：目标相互作用只会微妙地改变基因的活性。因此，要推断miRNAs如何与表型相关，进而与疾病相关，这并不是一件容易的事情。我们注意到，控制动物发育的主要信号转导级联是高度剂量敏感的，在人类疾病中经常发生变化。在此基础上，我们假设发育细胞信号通路是介导miRNA放松调控的一些主要表型后果的主要候选者，特别是在功能获得条件下。这一观点回顾了miRNA靶向主要信号通路的证据，并讨论了其对异常miRNA活性如何可能导致人类疾病和癌症的影响。
MicroRNAs (miRNAs) are critical post-transcriptional regulators that may collectively control a majority of animal genes. With thousands of miRNAs identified, a pressing challenge is now to understand their specific biological activities. Many predicted miRNA: target interactions only subtly alter gene activity. It has consequently not been trivial to deduce how miRNAs are relevant to phenotype, and by extension, relevant to disease. We note that the major signal transduction cascades that control animal development are highly dose-sensitive and frequently altered in human disorders. On this basis, we hypothesize that developmental cell signaling pathways represent prime candidates for mediating some of the major phenotypic consequences of miRNA deregulation, especially under gain-of-function conditions. This perspective reviews the evidence for miRNA targeting of the major signaling pathways, and discusses its implications for how aberrant miRNA activity might underlie human disease and cancer.