miRNA-21–3p targeting of FGF2 suppresses autophagy of bovine ovarian granulosa cells through AKT/mTOR pathway

Ma, Lizhu; Tang, Xiaorong; Guo, Shoudong; Liang, Mingyue; Zhang, Bin; Jiang, Zhongliang

doi:10.1016/j.theriogenology.2020.06.021

Cited by 22 publications

(10 citation statements)

References 56 publications

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“…With the increasing amount of documents, the study of follicular autophagy has attracted increasing attention. We have previously shown that the autophagy was observed in the BGC of large follicles, which was regulated by miR-21-3p through AKT/ mTOR pathway (Ma et al, 2020). A key autophagy-related gene, ATG7 plays a critical role in germ cell survival as fewer germ cells and primordial follicles were observed in the ovary of Atg7-deficient mice (Song et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Although studies have shown that granulosa cells (GC) are a critical determinant of follicular atresia as they undergo apoptosis (Krysko et al, 2008;Yu et al, 2004), some recent studies indicated that GC autophagy is also involved in follicular atresia, which is related to the decreased expression of Bcl-2 and the subsequent activation of caspase proteins (Kaipia & Hsueh, 1997;Ma et al, 2020). These findings highlighted that the death of GC leads to follicular atresia (Choi et al, 2011), but the molecular mechanism is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Activin A attenuates apoptosis of granulosa cells in atretic follicles through ERβ‐induced autophagy

Liu

Wang

Yao

et al. 2022

Reprod Domestic Animals

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It is well known that approximately 99% of ovarian follicles in mammals suffer from a degenerative process known as atresia, which is a huge waste of genetic resource in female animals. Studies have shown that activin A (ACT‐A) is located in ovarian granulosa cells and has different effects in granulosa cell depending on species. Although granulosa cells play a critical role during follicular atresia, the mechanism of action of ACT‐A in bovine ovarian granulosa cells (BGC) is poorly understood. In this study, we first determined the apoptosis of BGCs isolated from growth follicles and atretic follicles respectively. Then, BGC isolated from atretic follicles were used as a model to elucidate the role of ACT‐A in cattle ovary. The results showed that apoptosis occurred in both growing follicles and atretic follicles, and the percentage of apoptotic cells in atretic follicles was higher than that in growing follicles. The current results indicated that ACT‐A can attenuate apoptosis of BGC by maintaining the function of BGC in atretic follicles. Increased ERβ induced by ACT‐A promoted BGC autophagy but had no effect on apoptosis. In summary, this study suggests that ACT‐A attenuates BGC apoptosis in atretic follicles by ERβ‐mediated autophagy signalling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activin A attenuates apoptosis of granulosa cells in atretic follicles through ERβ‐induced autophagy

Liu

Wang

Yao

et al. 2022

Reprod Domestic Animals

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“…Downregulated FGF2 rescued the effects of silencing of miR‐497‐5p on apoptosis and autophagy in PD. Ma et al revealed that FGF2 is targeted by miR‐21‐3p and promotes the autophagy of bovine ovarian granulosa cells by the AKT/mTOR pathway 41 . Downregulation of FGF2 induces the inhibition of autophagy in nasopharyngeal cancer cells dependent on the AKT pathway 42 .…”

Section: Discussionmentioning

confidence: 99%

Silencing of miR‐497‐5p inhibits cell apoptosis and promotes autophagy in Parkinson's disease by upregulation of FGF2

Zhu

Hui

Gao

et al. 2021

Environmental Toxicology

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Parkinson's disease (PD) is a progressive neurodegenerative disorder with increasing prevalence in elderly individuals globally. MicroRNAs (miRNAs) have been confirmed to participate in the pathogenesis of various neurodegenerative diseases, including PD. MiR‐497‐5p is previously reported to be upregulated in PD. The present study was designed to further explore the function of miR‐497‐5p in PD. MiR‐497‐5p was significantly upregulated in 1‐methyl‐4‐phenylpyridinium (MPP+)‐treated SH‐SY5Y cells. Inhibition of miR‐497‐5p suppressed the cell apoptosis and triggered autophagy of MPP+‐treated SH‐SY5Y cells. Further, miR‐497‐5p targeted fibroblast growth factor‐2 (FGF2) in MPP+‐treated SH‐SY5Y cells. Subsequently, rescue assays revealed that miR‐497‐5p regulated apoptosis and autophagy of MPP+‐treated SH‐SY5Y cells by mediation on FGF2. In addition, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) induced PD mice models were established. The results exhibited that silencing of miR‐497‐5p improved mice bradykinesia, reduced cell apoptosis and induced autophagy in PD mice by FGF2. In conclusion, silencing of miR‐497‐5p alleviates PD by suppressing cell apoptosis and promoting autophagy in a FGF2 dependent manner, which will provide a novel target for Parkinson's disease management.

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“…Study done by Donadeu et al (43) reported higher expression of miR-21-5p/-3p in atretic than healthy follicles of cattle. In this context, studies reported the regulation of follicular atresia by miR-21-3p through targeting FGF2 (44) and VEGFA (45) that ultimately inhibits bovine granulosa cell autophagy by repressing AKT/mTOR signaling and PI3K/AKT signaling, respectively. Another study reported the higher expression of bta-miR-21-5p during early CL (1-7 days) as compared to middle CL and late CL (46), suggesting its role in the corpus luteum formation, functionalization, and corpus luteum regression (23).…”

Section: Discussionmentioning

confidence: 99%

Urinary Cell-Free miR-99a-5p as a Potential Biomarker for Estrus Detection in Buffalo

et al. 2021

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Accurate estrus detection method is the need of the hour to improve reproductive efficiency of buffaloes in dairy industry, as the currently available estrus detection methods/tools lack high sensitivity and specificity. Recently, circulating miRNAs have been shown as non-invasive biomarkers by various studies. Hence, in order to evaluate their potential as estrus biomarkers, the objective of this study was to identify and compare the levels of 10 hormone-responsive miRNAs in the urine collected at proestrus (PE), estrus (E), and diestrus (DE) phases of buffaloes (n = 3) pertaining to a discovery sample. Among 10 urinary miRNAs, the levels of bta-mir-99a-5p (E/PE 0.5-fold, P < 0.05; DE/PE 1.9-fold), bta-miR-125b (E/PE 0.5-fold; DE/PE 0.7-fold), bta-mir-145 (E/PE 1.5-fold; DE/PE 0.7-fold), bta-mir-210 (E/PE 1.2-fold, DE/PE 0.7-fold), mir-21 (E/PE 1.5-fold, DE/PE 2-fold), and bta-mir-191 (E/PE 1.3-fold; DE/PE 0.8-fold) were found to be altered during different phases of buffalo estrous cycle. In contrast, bta-mir-126-3p, bta-let-7f, bta-mir-16b, and bta-mir-378 were undetected in buffalo urine. Furthermore, a validation study in an independent group of 25 buffalo heifers showed the increased levels of urinary bta-mir-99a-5p during the DE (3.92-fold; P < 0.0001) phase as compared to the E phase. Receiver operating characteristic curve analyses also revealed the ability of urinary miR-99a-5p in distinguishing the E from the DE phase (area under the curve of 0.6464; P < 0.08). In silico analysis further showed an enrichment of miR-99a-5p putative targets in various ovarian signaling pathways, including androgen/estrogen/progesterone biosynthesis and apoptosis signaling, implicating the role of miR-99a-5p in ovarian physiology. In conclusion, significantly lower levels of bta-mir-99a-5p at the E phase than the DE phase in buffalo urine indicate its biomarker potential, which needs to be further explored in a large cohort in the future studies.

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miRNA-21–3p targeting of FGF2 suppresses autophagy of bovine ovarian granulosa cells through AKT/mTOR pathway

Cited by 22 publications

References 56 publications

Activin A attenuates apoptosis of granulosa cells in atretic follicles through ERβ‐induced autophagy

Activin A attenuates apoptosis of granulosa cells in atretic follicles through ERβ‐induced autophagy

Silencing of miR‐497‐5p inhibits cell apoptosis and promotes autophagy in Parkinson's disease by upregulation of FGF2

Urinary Cell-Free miR-99a-5p as a Potential Biomarker for Estrus Detection in Buffalo

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