miR-23a and miR-27a Promote Human Granulosa Cell Apoptosis by Targeting SMAD51

Nie, Mingyue; Yu, Shun; Peng, Sha; Fang, Ying; Wang, Hongmei; Yang, Xiaokui

doi:10.1095/biolreprod.115.130690

Cited by 92 publications

(69 citation statements)

References 43 publications

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“…Much of the existing evidence has been obtained using follicular cell cultures, mostly granulosa cells. Often reported effects of miRNAs include either the promotion or suppression of granulosa cell apoptosis [5], [6], [7], [8], [9], [10]. Yet, in many cases, the site of expression, if any, of these miRNAs within follicles (ie, granulosa and theca compartments) or whether their expression actually changes during follicle atresia, supporting their physiological role, has not been clarified.…”

Section: Introductionmentioning

confidence: 99%

A miRNA target network putatively involved in follicular atresia

Donadeu

Mohammed

Ioannidis

2017

Domestic Animal Endocrinology

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In a previous microarray study, we identified a subset of micro RNAS (miRNAs), which expression was distinctly higher in atretic than healthy follicles of cattle. In the present study, we investigated the involvement of those miRNAs in granulosa and theca cells during atresia. Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) confirmed that miR-21-5p/-3p, miR-150, miR-409a, miR-142-5p, miR-378, miR-222, miR-155, and miR-199a-5p were expressed at higher levels in atretic than healthy follicles (9–17 mm, classified based on steroidogenic capacity). All miRNAs except miR-21-3p and miR-378 were expressed at higher levels in theca than granulosa cells. The expression of 13 predicted miRNA targets was determined in follicular cells by RT-qPCR, revealing downregulation of HIF1A, ETS1, JAG1, VEGFA, and MSH2 in either or both cell types during atresia. Based on increases in miRNA levels simultaneous with decreases in target levels in follicular cells, several predicted miRNA target interactions were confirmed that are putatively involved in follicular atresia, namely miR-199a-5p/miR-155-HIF1A in granulosa cells, miR-155/miR-222-ETS1 in theca cells, miR-199a-5p-JAG1 in theca cells, miR-199a-5p/miR-150/miR-378-VEGFA in granulosa and theca cells, and miR-155-MSH2 in theca cells. These results offer novel insight on the involvement of miRNAs in follicle development by identifying a miRNA target network that is putatively involved in follicle atresia.

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Section: Introductionmentioning

confidence: 99%

A miRNA target network putatively involved in follicular atresia

Donadeu

Mohammed

Ioannidis

2017

Domestic Animal Endocrinology

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“…In plasma of premature ovarian failure (POF) patients, miR-23a has been found to decrease X-linked inhibitor of apoptosis protein (XIAP) expression (at the mRNA and protein levels) with a simultaneous increase of cleaved caspase-3 protein [17], thereby increasing apoptosis in GCs. Consistent with this, miR-23a and miR-27a have been shown to promote human granulose cell apoptosis in vitro by directly targeting SMAD5 [49]. In this regard, these miRNAs are acting as pro-apoptotic and apoptotic factors in pathological and normal cycling cells, respectively.…”

Section: Functional Roles Of Mirnas During Follicular Cellular Apomentioning

confidence: 66%

“…The Fas ligand (FasL-Fas) system is one of the well-defined apoptotic signaling pathways known to play an indispensable role during follicular atresia [33,34,38]. The FasL-Fas signaling pathway also modulates the apoptotic role of miR-23a and -27a by downregulating the protein expression level of the target gene smad5 [49]. In several studies, the transforming growth factor beta signaling (TGF-β) pathway appears to control cellular physiological processes associated with mammalian reproduction [68,69,70].…”

Section: Molecular Signaling Pathways Enriched In Mirna-mediated Fmentioning

confidence: 99%

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MicroRNAs: New Insight in Modulating Follicular Atresia: A Review

Worku

Rehman

Talpur

et al. 2017

IJMS

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Our understanding of the post-transcriptional mechanisms involved in follicular atresia is limited; however, an important development has been made in understanding the biological regulatory networks responsible for mediating follicular atresia. MicroRNAs have come to be seen as a key regulatory actor in determining cell fate in a wide range of tissues in normal and pathological processes. Profiling studies of miRNAs during follicular atresia and development have identified several putative miRNAs enriched in apoptosis signaling pathways. Subsequent in vitro and/or in vivo studies of granulosa cells have elucidated the functional role of some miRNAs along with their molecular pathways. In particular, the regulatory roles of some miRNAs have been consistently observed during studies of follicular cellular apoptosis. Continued work should gradually lead to better understanding of the role of miRNAs in this field. Ultimately, we expect this understanding will have substantial benefits for fertility management at both the in vivo or/and in vitro levels. The stable nature of miRNA holds remarkable promise in clinical use as a diagnostic tool and in reproductive medicine to solve the ever-increasing fertility problem. In this review, we summarize current knowledge of the involvement of miRNAs in follicular atresia, discuss the challenges for further work and pinpoint areas for future research.

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“…The two paralogous clusters reside on different chromosomes and are transcribed independently, and it is likely they undergo different mechanisms of regulation. The biological functions of the mirn23a cluster have been shown to play a role in a wide variety of processes, including hematopoietic development 16,17,18 , apoptosis 19,20 , drug resistance 21 , tumor suppression 22 , and oncogenesis 23,24,25,26 . Functional studies been performed to show that overexpression of miR-23a, miR-24-2, or miR-27a individually lead to entirely different phenotypic results than the entire mir23a cluster, demonstrating the importance of studying the cluster in its entirety 27 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the mirn23a Cluster through an iTRAQ-based Quantitative Proteomic Approach

2016

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MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that are implicated in a number of disease states. MiRNAs can exist as individual entities, or may be clustered and transcribed as a single polycistron. The mirn23a cluster consists of three miRNAs, miR-23a, miR-24-2, and miR-27a. While these miRNAs are transcribed together, they often exist at varying levels in the cell. Despite the fact that the mirn23a cluster is known to play a role in a number of diseases and developmental processes, few direct targets have been identified. In this study, we examined the effects of miR-23a, miR-24-2, miR-27a, or the mirn23a cluster overexpression on the proteome of 70Z/3 pre-B lymphoblast cells. Quantitative mass spectrometry using isobaric tags for relative and absolute quantification (iTRAQ) allowed for global profiling of cell lines after miRNA overexpression. We identified a number of targets of each miRNA that contained predicted miRNA seed sequences and are likely direct targets. In addition, we discovered a cohort of shared miRNA targets and cluster targets, demonstrating the importance of studying miRNA clusters in their entirety.

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miR-23a and miR-27a Promote Human Granulosa Cell Apoptosis by Targeting SMAD51

Cited by 92 publications

References 43 publications

A miRNA target network putatively involved in follicular atresia

A miRNA target network putatively involved in follicular atresia

MicroRNAs: New Insight in Modulating Follicular Atresia: A Review

Evaluation of the mirn23a Cluster through an iTRAQ-based Quantitative Proteomic Approach

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