Combinatorial microRNAs Working together to make a difference
Combinatorial microRNAs Working together to make a difference
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DOI：
10.4161/cc.7.20.6923
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发表时间：
2008-10-15
期刊：
影响因子：
4.3
通讯作者：
Cleary, Michele A.
中科院分区：
文献类型：
--
作者：
Ivanovska, Irena;Cleary, Michele A.
microrna调节基因网络，因此本质上是复杂的。microrna本身在其他microrna的网络中起作用，其中一些microrna在同一位点共表达。为了更好地理解microrna之间的相互作用，我们研究了内源性和外源性共表达microrna的组合效应。在这篇综述中，我们首先提炼了在细胞分裂中起作用的三个microRNA家族，miR-16， miR-34a和miR-106b之间的异同，并强调了它们精致的表型多样性。鉴于microrna通过不同的靶点影响细胞周期进程，我们测试了它们之间的表型协同作用。此外，我们研究了单个和集合microrna的靶调控，以深入了解来自同一染色体位点共表达的microrna之间的相互作用。microRNA在分子通路中调节多个基因的能力产生了一种思考靶向通路的新方式：而不是一个抑制剂-一个靶标模型，途径中的多个成分可以被一个microRNA调节，从而导致通路的有效且可逆的抑制。为了充分实现这一潜力，我们需要了解microrna如何单独发挥作用，以及如何相互协同作用。
MicroRNAs regulate gene networks and therefore are inherently complex. MicroRNAs themselves function in networks of other microRNAs, some of which are co-expressed from the same locus. To better understand the interplay among microRNAs that underlies their functions, we examined the potential of combinatorial effects of endogenously and exogenously co-expressed microRNAs. In this review, we first distill the similarities and differences between three microRNA families that function in cell division, miR-16, miR-34a and miR-106b, with emphasis on their exquisite phenotypic diversity. Given that the microRNAs affect cell cycle progression via distinct targets, we tested for phenotypic synergism among them. Furthermore, we investigate target regulation by individual and pooled microRNAs to gain insight into interactions among microRNAs co-expressed from the same chromosomal locus. The ability of microRNAs to modulate multiple genes within a molecular pathway engenders a novel way of thinking about targeting pathways: instead of a one-inhibitor-one-target model, multiple components in a pathway can be modulated by a microRNA resulting in a potent yet reversible inhibition of the pathway. To fully realize this potential, we need to understand how microRNAs function singly and in concert with each other.