MicroRNA-133b stimulates ovarian estradiol synthesis by targeting Foxl2
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- 作者：Anyi Dai ; Haixiang Sun ; Ting Fang ; Qun Zhang ; Shaogen Wu ; Yue Jiang ; Lijun Ding ; Guijun Yan ; Yali Hu
- 关键词：Foxl2 ; forkhead L2 ; miR-133b ; microRNA-133b ; StAR ; steroidogenic acute regulatory protein ; CYP ; cytochrome P450 ; 3&prime ; UTR ; 3&prime ; untranslated region ; POF ; premature ovarian failure ; FSH ; follicle-stimulating hormone ; ACVRIB ; activin receptor typeIB
- 刊名：FEBS Letters
- 出版年：2013
- 出版时间：2 August, 2013
- 年：2013
- 卷：587
- 期：15
- 页码：2474-2482
- 全文大小：2135 K
文摘
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¡ä untranslated region (3¡äUTR) 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¡äUTR, thus inhibiting the Foxl2-mediated transcriptional repression of StAR and CYP19A1to promote estradiol production.