Chi-miR-4110 promotes granulosa cell apoptosis by targeting Sma- and Mad-related protein 2 (Smad2) in the caprine ovary

An, Xiaopeng; Song, Yuxuan; Hou, Jinxing; Zhang, Yue; Chen, Kaiwen; Ma, Haidong; Zhao, Xinyan; Li, Guang; Gao, Kun; Wang, Shan; Cao, Binyun; Bai, Yueyu

doi:10.1371/journal.pone.0181162

Cited by 13 publications

(5 citation statements)

References 41 publications

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“…MiR-4110 induces GC apoptosis via targeting SMAD2, and the ratio of an apoptosis index, Bcl-2-associated X protein (BAX)/B-cell CLL/Lyphoma 2 (BCL2), is also up-regulated in miR-4110 overexpressing GCs. Thus, MiR-4110 promotes GC apoptosis by targeting SMAD2 in the ovary (76). MiR-23a and miR-27a promotes apoptosis in human GC by targeting SMAD5 in the Fas ligand (FasL)-Fas signaling pathway (77).…”

Section: Physiological Conditionsmentioning

confidence: 99%

The Role of microRNAs in Ovarian Granulosa Cells in Health and Disease

Cheung

Chan³

et al. 2019

Front. Endocrinol.

102

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The granulosa cell (GC) is a critical somatic component of the ovary. It is essential for follicle development by supporting the developing oocyte, proliferating and producing sex steroids and disparate growth factors. Knowledge of the GC's function in normal ovarian development and function, and reproductive disorders, such as polycystic ovary syndrome (PCOS) and premature ovarian failure (POF), is largely acquired through clinical studies and preclinical animal models. Recently, microRNAs have been recognized to play important regulatory roles in GC pathophysiology. Here, we examine the recent findings on the role of miRNAs in the GC, including four related signaling pathways (Transforming growth factor-β pathway, Follicle-stimulating hormones pathway, hormone-related miRNAs, Apoptosis-related pathways) and relevant diseases. Therefore, miRNAs appear to be important regulators of GC function in both physiological and pathological conditions. We suggest that targeting specific microRNAs is a potential therapeutic option for treating ovary-related diseases, such as PCOS, POF, and GCT.

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Section: Physiological Conditionsmentioning

confidence: 99%

The Role of microRNAs in Ovarian Granulosa Cells in Health and Disease

Cheung

Chan³

et al. 2019

Front. Endocrinol.

102

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“…In these cells, miR‐375 targets SP1 to block cell growth. However, in the caprine ovary, SP1 causes FGC apoptosis by increasing p53 and Bax (An et al, 2017). STAT3 strengthens the anti‐apoptotic and proliferative effects in porcine FGCs (Yuan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

miR‐21, miR‐125b, and let‐7b contribute to the involution of atretic follicles and corpus lutea in Tibetan sheep ovaries

Zhang

Huo

Wei

et al. 2022

Animal Science Journal

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Follicular granulosa cells (FGCs) are crucial for ovarian follicle functions, and miRNAs are differentially expressed at various stages of follicular developments. In this study, we confirmed that miR-21, miR-125b, and let-7b were located in FGCs/luteal cells by in situ hybridization experiments. Moreover, miR-21 and miR-125b expressions were upregulated in late corpus lutea (CL) and atretic follicles (AF); let-7b expression was increased in early AF. After transfected with inhibitor or mimic of miRNAs in FGCs, we found that FGCs apoptosis was decreased in the miR-21-mi group but increased in the miR-125b-mi group using flow cytometry. mRNA and protein expression levels were determined for apoptosis-related factors (e.g., Bcl-2 and Bax), the potential target genes of miRNAs (e.g., SMAD7, SP1, and STAT3), hormone receptors (e.g., FSHR and LHR), and genes related to hormone secretion (e.g., CYP19, CYP11, and 3βHSD). The protein levels of SMAD7 were decreased in the miR-21-mi group but opposite to SP1 and FSHR. In the let-7b-mi group, Bcl-2, SMAD7, and FSHR were suppressed but not Bax, CYP11, and 3βHSD. However, hormone secretion was not changed in the supernatant of transfected FGCs. This study provides information about ovarian miRNAs to improve the fertility in Tibetan sheep.

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“…For receptors, let-7g and miR-202-5p induce GC apoptosis by inhibiting pig TGF-β1 and goat TGF-β1 , respectively [ 55 , 56 ]. For SMADs, miR-4110 promotes goat GC apoptosis by inhibiting SMAD2 [ 57 ], and miR-224 controls mouse GC proliferation and estradiol release by inhibiting Smad4 [ 50 ]. Herein, we showed for the first time that miRNA activates the TGF-β signaling pathway to reduce GC apoptosis by target directly activating a core component of this pathway.…”

Section: Discussionmentioning

confidence: 99%

miR-2337 induces TGF-β1 production in granulosa cells by acting as an endogenous small activating RNA

Wang

et al. 2021

Cell Death Discov.

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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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Chi-miR-4110 promotes granulosa cell apoptosis by targeting Sma- and Mad-related protein 2 (Smad2) in the caprine ovary

Cited by 13 publications

References 41 publications

The Role of microRNAs in Ovarian Granulosa Cells in Health and Disease

The Role of microRNAs in Ovarian Granulosa Cells in Health and Disease

miR‐21, miR‐125b, and let‐7b contribute to the involution of atretic follicles and corpus lutea in Tibetan sheep ovaries

miR-2337 induces TGF-β1 production in granulosa cells by acting as an endogenous small activating RNA

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