miR-18, a member of Oncomir-1, targets heat shock transcription factor 2 in spermatogenesis
miR-18, a member of Oncomir-1, targets heat shock transcription factor 2 in spermatogenesis
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DOI：
10.1242/dev.050955
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发表时间：
2010-10-01
期刊：
影响因子：
4.6
通讯作者：
Sistonen, Lea
中科院分区：
文献类型：
--
作者：
Bjork, Johanna K.;Sandqvist, Anton;Sistonen, Lea
miR-18属于与不同类型癌症的发生和进展密切相关的Oncomir-1或类似于92的miR-17簇。然而，Oncomir-1簇及其单个mirna的生理作用在很大程度上是未知的。在这里，我们描述了miR-18在小鼠中的一种新功能。我们发现miR-18直接靶向热休克因子2 (HSF2)，这是一种影响包括胚胎发生和配子体发生在内的广泛发育过程的转录因子。此外，我们发现miR-18在睾丸中高度丰富，在构成精子发生的上皮周期中表现出不同的细胞类型特异性表达。在精子发生过程中，HSF2和miR-18的表达呈负相关，表明在生殖细胞中，HSF2被miR-18下调。为了研究miR-18在体内的功能，我们开发了一种新的方法，T-GIST，并证明在完整的精小管中抑制miR-18可导致HSF2蛋白水平升高和HSF2靶基因表达改变。我们的研究结果表明，miR-18调节HSF2在精子发生中的活性，并将miR-18与HSF2介导的生理过程（如男性生殖细胞成熟）联系起来。
miR-18 belongs to the Oncomir-1 or miR-17 similar to 92 cluster that is intimately associated with the occurrence and progression of different types of cancer. However, the physiological roles of the Oncomir-1 cluster and its individual miRNAs are largely unknown. Here, we describe a novel function for miR-18 in mouse. We show that miR-18 directly targets heat shock factor 2 (HSF2), a transcription factor that influences a wide range of developmental processes including embryogenesis and gametogenesis. Furthermore, we show that miR-18 is highly abundant in testis, displaying distinct cell-type-specific expression during the epithelial cycle that constitutes spermatogenesis. Expression of HSF2 and of miR-18 exhibit an inverse correlation during spermatogenesis, indicating that, in germ cells, HSF2 is downregulated by miR-18. To investigate the in vivo function of miR-18 we developed a novel method, T-GIST, and demonstrate that inhibition of miR-18 in intact seminiferous tubules leads to increased HSF2 protein levels and altered expression of HSF2 target genes. Our results reveal that miR-18 regulates HSF2 activity in spermatogenesis and link miR-18 to HSF2-mediated physiological processes such as male germ cell maturation.