miR-2337 induces TGF-β1 production in granulosa cells by acting as an endogenous small activating RNA.
miR-2337 induces TGF-β1 production in granulosa cells by acting as an endogenous small activating RNA.
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miR-2337 通过充当内源性小激活 RNA 诱导颗粒细胞中 TGF-β1 的产生
DOI：
10.1038/s41420-021-00644-4
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发表时间：
2021-09-18
影响因子：
7
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Wang L;Du X;Li Q;Wu W;Pan Z;Li Q
转化生长因子-β-1是哺乳动物卵巢功能和雌性生育所必需的。在此，我们在猪 - 13‘- 中发现了三个完全连锁的变异体，包括两个已知的变异体c.1583A >； G和c.1587A >； G以及新的变异体c.2074A >； C。揭示了这些变异在约克夏母猪繁殖力中的重要作用。突变c.1583A >； G和c.1587A >； G位于miR-2337的miRNA反应元件上，影响miR-2337对转化生长因子-β1 3‘-非编码区活性的调节。有趣的是，miR-2337诱导而不是减少颗粒细胞(GC)中转化生长因子-β1的转录和产生。在机制上，miR-2337通过核心启动子区域的MRE基序增强转化生长因子-β1启动子的活性，并改变组蛋白修饰，包括H3K4me2、H3K4me3、H3K9me2和H3K9ac。此外，miR-2337还控制转化生长因子-β1介导的转化生长因子-β信号通路的活性和胃癌细胞的凋亡。综上所述，我们的研究结果确定miR-2337是GCs中转化生长因子-β1的内源性小激活核糖核酸(SARNA)，而miR-2337是转化生长因子-β信号通路的小激活因子，有望成为挽救胃癌细胞凋亡和治疗低生育能力的新靶点。
Transforming growth factor-β1 (TGF-β1) is essential for ovarian function and female fertility in mammals. Herein, we identified three completely linked variants, including two known variants referred to as c.1583A > G and c.1587A > G and the novel variant c.2074A > C in the porcine TGF-β1 3′-UTR. An important role of these variants in Yorkshire sow fertility was revealed. Variants c.1583A > G and c.1587A > G were located at the miRNA response element (MRE) of miR-2337 and affected miR-2337 regulation of TGF-β1 3′-UTR activity. Interestingly, miR-2337 induces, not reduces the transcription and production of TGF-β1 in granulosa cells (GCs). Mechanistically, miR-2337 enhances TGF-β1 promoter activity via the MRE motif in the core promoter region and alters histone modifications, including H3K4me2, H3K4me3, H3K9me2, and H3K9ac. In addition, miR-2337 controls TGF-β1-mediated activity of the TGF-β signaling pathway and GC apoptosis. Taken together, our findings identify miR-2337 as an endogenous small activating RNA (saRNA) of TGF-β1 in GCs, while miR-2337 is identified as a small activator of the TGF-β signaling pathway which is expected to be a new target for rescuing GC apoptosis and treating low fertility.
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影响因子：
2.4
作者：
Marhemati, Farnaz;Rezaei, Ramazan;Amani, Davar
通讯作者：
Amani, Davar
SMAD4 反馈调节经典 TGF-β 信号通路以控制颗粒细胞凋亡
影响因子：
9
作者：
Du X;Pan Z;Li Q;Liu H;Li Q
通讯作者：
Li Q
影响因子：
6.7
作者：
Fried, G;Wramsby, H;Tally, M
通讯作者：
Tally, M
影响因子：
3.6
作者：
GRAHAM, CH;LYSIAK, JJ;LALA, PK
通讯作者：
LALA, PK
DOI：
10.1038/s41580-018-0007-0
发表时间：
2018-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
David CJ;Massagué J
通讯作者：
Massagué J