Cohen Amit, Shmoish Michael, Levi Liraz, Cheruti Uta, Levavi-Sivan Berta, Lubzens Esther
Department of Marine Biology, Israel Oceanographic and Limnological Research, Haifa, Israel.
Endocrinology. 2008 Apr;149(4):1687-96. doi: 10.1210/en.2007-0969. Epub 2007 Dec 20.
Estrogens are steroid hormones that have been implicated in a variety of cellular and physiological processes in the development of diseases such as cancer and are also known to be associated with the effects of endocrine disrupting chemicals. Here we show that 17beta-estradiol (E(2)) alters microRNA (miRNA) expression profiles in the adult zebrafish (Danio rerio). An association between E(2) and the expression of 25 miRNAs was found 12 h after treatment. Among the most up-regulated miRNAs were miR-196b and let-7h, and the most down-regulated miRNAs included miR-130c and miR-101a. Tissue-specific changes in the transcripts levels of estrogen receptors (Esr1, Esr2a, and Esr2b) and miRNAs were found after hormone treatment. The most up-regulated miR-196b and its precursors are highly expressed in the skin and showed similar tissue-specific expression patterns after treatment, indicating a common pattern of regulation by E(2). MiR-196b was shown to fine-tune the expression of its target gene Hoxb8a after treatment in whole-body homogenates. Taken together, our results suggest a novel pathway for the multifunctional and pleiotropic effects of estrogens and open new directions for future investigations of their association with miRNAs involved in estrogen-regulated physiological processes and diseases.
雌激素是类固醇激素，与癌症等疾病发展过程中的多种细胞和生理过程有关，并且已知与内分泌干扰化学物质的作用相关。在此我们表明，17β-雌二醇（E₂）会改变成年斑马鱼（Danio rerio）中的微小RNA（miRNA）表达谱。处理12小时后发现E₂与25种miRNA的表达之间存在关联。上调最显著的miRNA包括miR-196b和let-7h，下调最显著的miRNA包括miR-130c和miR-101a。激素处理后发现雌激素受体（Esr1、Esr2a和Esr2b）和miRNA的转录水平存在组织特异性变化。上调最显著的miR-196b及其前体在皮肤中高度表达，处理后显示出相似的组织特异性表达模式，表明E₂存在共同的调控模式。在全身匀浆中处理后，miR-196b被证明可微调其靶基因Hoxb8a的表达。综上所述，我们的结果提示了雌激素多功能和多效性作用的一条新途径，并为未来研究其与参与雌激素调节的生理过程和疾病的miRNA之间的关联开辟了新方向。
