MicroRNA-133b stimulates ovarian estradiol synthesis by targeting Foxl2
MicroRNA-133b stimulates ovarian estradiol synthesis by targeting Foxl2
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MicroRNA-133b 通过靶向 Foxl2 刺激卵巢雌二醇合成
DOI：
10.1016/j.febslet.2013.06.023
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发表时间：
2013-08-02
期刊：
影响因子：
3.5
通讯作者：
Hu, Yali
中科院分区：
文献类型：
--
作者：
Dai, Anyi;Sun, Haixiang;Hu, Yali
Forkhead L2(FOXL2)在卵巢颗粒细胞中表达，通过转录调控类固醇生成急性调节蛋白(STAR)和细胞色素P19A1等靶基因参与类固醇的合成。在本研究中，我们建立了microRNA-133b(miR-133b)与FOXL2介导的颗粒细胞雌二醇释放之间的直接联系。MIR-133b参与了卵泡刺激素(FSH)诱导的雌激素生成。荧光素酶分析证实miR-133b与FOXL2mRNA的3‘非翻译区(3’UTR)结合。与这一发现一致的是，miR-133b过表达降低了FOXL2水平。此外，miR-133b抑制FOXL2与STAR和CYP19A1启动子序列的结合。这些结果表明，miR-133b通过直接靶向3‘端非编码区，下调颗粒细胞FOXL2的表达，从而抑制FOXL2介导的STAR和CYP19A1的转录抑制，促进雌二醇的产生。皇冠版权所有(C)2013，由爱思唯尔公司代表欧洲生化学会联合会出版。版权所有。
Forkhead L2 (Foxl2) is expressed in ovarian granulosa cells and participates in steroidogenesis by transcriptionally regulating target genes such as steroidogenic acute regulatory protein (StAR) and CYP19A1. In this study, a direct link between microRNA-133b (miR-133b) and Foxl2-mediated estradiol release in granulosa cells was established. miR-133b was involved in follicle-stimulating hormone (FSH)-induced estrogen production. Luciferase assays confirmed that miR-133b was bound to the 3' untranslated region (3'UTR) of Foxl2 mRNA. Consistent with this finding, miR-133b overexpression reduced the Foxl2 levels. Furthermore, miR-133b inhibited Foxl2 binding to the StAR and CYP19A1 promoter sequences. These results demonstrate that miR-133b down-regulates Foxl2 expression in granulosa cells by directly targeting the 3'UTR, thus inhibiting the Foxl2-mediated transcriptional repression of StAR and CYP19A1 to promote estradiol production. Crown Copyright (C) 2013 Published by Elsevier B.V. on behalf of Federation of European Biochemical society. All rights reserved.