Zhang Li, Zhang XiaoXin, Zhang Xuejing, Lu Yu, Li Lei, Cui Sheng
State Key Laboratory of AgrobiotechnologyCollege of Biological Sciences, China Agricultural University, People's Republic of China.
State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of Zoology, Chinese Academy of Sciences, China University of Chinese Academy of Sciences, Beijing, People's Republic of China.
J Endocrinol. 2017 Jul;234(1):1-14. doi: 10.1530/JOE-16-0488.
MicroRNAs (MiRNAs) play important regulatory roles in many cellular processes. MiR-143 is highly enriched in the mouse ovary, but its roles and underlying mechanisms are not well understood. In the current study, we show that miR-143 is located in granulosa cells of primary, secondary and antral follicles. To explore the specific functions of miR-143, we transfected miR-143 inhibitor into primary cultured granulosa cells to study the loss of function of miR-143 and the results showed that miR-143 silencing significantly increased estradiol production and steroidogenesis-related gene expression. Moreover, our and studies showed that follicular stimulating hormone (FSH) significantly decreased miR-143 expression. This function of miR-143 is accomplished by its binding to the 3'-UTR of mRNA. Furthermore, our results demonstrated that miR-143 acts as a negative regulating molecule mediating the signaling pathway of FSH and affecting estradiol production by targeting KRAS. MiR-143 also negatively acts in regulating granulosa cells proliferation and cell cycle-related genes expression. These findings indicate that miR-143 plays vital roles in FSH-induced estradiol production and granulosa cell proliferation, providing a novel mechanism that involves miRNA in regulating granulosa cell functions.
微小RNA（miRNA）在许多细胞过程中发挥着重要的调节作用。miR-143在小鼠卵巢中高度富集，但其作用及潜在机制尚未完全明确。在本研究中，我们发现miR-143定位于初级、次级和窦状卵泡的颗粒细胞中。为探究miR-143的具体功能，我们将miR-143抑制剂转染至原代培养的颗粒细胞中，以研究miR-143的功能丧失情况，结果显示miR-143沉默显著增加了雌二醇的产生以及类固醇生成相关基因的表达。此外，我们的研究表明促卵泡激素（FSH）显著降低了miR-143的表达。miR-143的这一功能是通过其与mRNA的3'-UTR结合来实现的。此外，我们的结果表明miR-143作为一种负调节分子，通过靶向KRAS介导FSH信号通路并影响雌二醇的产生。miR-143在调节颗粒细胞增殖和细胞周期相关基因表达方面也发挥着负向作用。这些发现表明miR-143在FSH诱导的雌二醇产生和颗粒细胞增殖中起着至关重要的作用，为miRNA参与调节颗粒细胞功能提供了一种新机制。
