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首页> 外文期刊>Domestic Animal Endocrinology >Upregulation of miR-146b promotes porcine ovarian granulosa cell apoptosis by attenuating CYP19A1
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Upregulation of miR-146b promotes porcine ovarian granulosa cell apoptosis by attenuating CYP19A1

机译：MiR-146B的上调通过衰减CYP19A1促进猪卵巢颗粒细胞细胞凋亡

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摘要

MicroRNAs (miRNAs) are 21- to 24-nucleotide long small noncoding RNAs, which play an important role in follicular atresia and granulosa cell (GC) apoptosis in the mammalian ovary. Here, we report that miR-146b, a conserved and ovary-enriched miRNA, modulates estradiol (E2) secretion, GC apoptosis, and follicular atresia in pigs. Genome-wide analysis and quantitative real-time PCR revealed that miR-146b was significantly upregulated during follicular atresia, and fluorescence-activated cell sorting showed that miR-146b functioned as a proapoptotic factor to induce GC apoptosis. MicroRNA-mRNA network analysis and luciferase reporter assays showed that CYP19A1, the pivotal enzyme for E2 synthesis signaling, was directly targeted by miR-146b. Furthermore, miR-146b interacted with the 3'untranslated region of CYP19A1 to prevent translation, thereby regulating CYP19A1-mediated E2 secretion and GC apoptosis. However, miR-146b was not regulated by the transcription factor SMAD4 or oxidative stress, both of which are critical regulators of CYP19A1. We, thus, conclude that miR-146b is a novel epigenetic factor regulating GC functions, follicular development, and female reproduction. (C) 2020 Elsevier Inc. All rights reserved.
机译：microRNA（miRNA）是一种长度为21-24个核苷酸的非编码小RNA，在哺乳动物卵巢卵泡闭锁和颗粒细胞（GC）凋亡中起重要作用。在这里，我们报告miR-146b是一种保守且富含卵巢的miRNA，可调节猪的雌二醇（E2）分泌、GC凋亡和卵泡闭锁。全基因组分析和实时定量PCR显示miR-146b在卵泡闭锁期间显著上调，荧光激活细胞分选显示miR-146b作为促凋亡因子诱导GC凋亡。MicroRNA mRNA网络分析和荧光素酶报告分析表明，E2合成信号的关键酶CYP19A1直接被miR-146b靶向。此外，miR-146b与CYP19A1的3'非翻译区相互作用以阻止翻译，从而调节CYP19A1介导的E2分泌和GC凋亡。然而，miR-146b不受转录因子SMAD4或氧化应激的调节，两者都是CYP19A1的关键调节因子。因此，我们得出结论，miR-146b是一种新的表观遗传因子，调节GC功能、卵泡发育和雌性生殖。（C） 2020爱思唯尔公司版权所有。

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