Transactivation of miR-202-5p by Steroidogenic Factor 1 (SF1) Induces Apoptosis in Goat Granulosa Cells by Targeting TGFβR2

被引：25
作者：
Ding, Qiang [1 ]
Jin, Miaohan [1 ]
Wang, Yaoyue [1 ]
Liu, Jiao [1 ]
Kalds, Peter [1 ]
Wang, Ying [1 ]
Yang, Yuxin [1 ]
Wang, Xiaolong [1 ]
Chen, Yulin [1 ]
机构：
[1] Northwest A&F Univ, Key Lab Anim Genet Breeding & Reprod Shaanxi Prov, Coll Anim Sci & Technol, Yangling 712100, Shaanxi, Peoples R China
来源：
CELLS | 2020年 / 9卷 / 02期
关键词：
miR-202-5p; TGF beta R2; TGF-beta signaling pathway; goat granulosa cell; cell apoptosis; SF1; TGF-BETA RECEPTORS; DIFFERENTIALLY EXPRESSED GENES; GROWTH-FACTOR; ATRESIA; CYTOCHROME-P-450; FOLLICLES; MECHANISM; DEATH;
D O I：
10.3390/cells9020445
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
MicroRNAs play key roles during ovary development, with emerging evidence suggesting that miR-202-5p is specifically expressed in female animal gonads. Granulosa cells (GCs) are somatic cells that are closely related to the development of female gametes in mammalian ovaries. However, the biological roles of miR-202-5p in GCs remain unknown. Here, we show that miR-202-5p is specifically expressed in GCs and accumulates in extracellular vesicles (EVs) from large growth follicles in goat ovaries. In vitro assays showed that miR-202-5p induced apoptosis and suppressed the proliferation of goat GCs. We further revealed that miR-202-5p is a functional miRNA that targets the transforming growth factor-beta type II receptor (TGF beta R2). MiR-202-5p attenuated TGF-beta/SMAD signaling through the degradation of TGF beta R2 at both the mRNA and protein level, decreasing p-SMAD3 levels in GCs. Moreover, we verified that steroidogenic factor 1 (SF1) is a transcriptional factor that binds to the promoters of miR-202 and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) through luciferase reporter and chromatin immunoprecipitation (ChIP) assays. That contributed to positive correlation between miR-202-5p and CYP19A1 expression and estradiol (E2) release. Furthermore, SF1 repressed TGF beta R2 and p-SMAD3 levels in GCs through the transactivation of miR-202-5p. Taken together, these results suggest a mechanism by which miR-202-5p regulates canonical TGF-beta/SMAD signaling through targeting TGF beta R2 in GCs. This provides insight into the transcriptional regulation of miR-202 and CYP19A1 during goat ovarian follicular development.
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页数：16
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