miR‐375 negatively regulates porcine preadipocyte differentiation by targeting <scp>BMPR</scp>2

Liu, Siyuan; Sun, Guoxiang; Yuan, Bao; Zhang, Lianjiang; Gao, Yan; Jiang, Hao; Dai, Li-Shang; Zhang, Jiabao

doi:10.1002/1873-3468.12169

Cited by 32 publications

(31 citation statements)

References 43 publications

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“…Therefore, in light of the presented experimental results, we speculate that in bovine CCs cultured in vitro, the GDF9/BMP15 heterodimer may bind to BMPR2-ALK7-ALK6 to form a receptor complex and induce SMAD2/3 phosphorylation and thereby regulate the expression of CC expansion-associated genes (PTX3/HAS2/PTGS2). BMPR2 is a target gene of miR-375 [29]. Thus, miR-375 regulates the elevation and reduction of BMPR2 expression and thereby modulates the SMAD2/3 pathway involving the GDF9/BMP15 heterodimer, affecting the proliferation and apoptosis of bovine CCs.…”

Section: Discussionmentioning

confidence: 99%

“…While the synergy interaction of BMP15/GDF9 or GDF9 alone is known to activate SMAD2/3 signaling, the mechanism and the involved genes by which BMP15/GDF9 produces an effect in bovine CCs remains unknown. Furthermore, our previous studies found that BMPR2 is a direct target of miR-375 in bovine cumulus cells [29]. While the individual or synergistic effect of BMP15/ GDF9 requires binding to BMPR2, the mechanism by which miR-375 regulate BMPR2 expression and thereby balance the effect of BMP15/GDF9 has yet to be determined.…”

Section: Introductionmentioning

confidence: 98%

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Regulatory Role of miRNA-375 in Expression of BMP15/GDF9 Receptors and its Effect on Proliferation and Apoptosis of Bovine Cumulus Cells

Chen

Liu

Jiang

et al. 2017

Cell Physiol Biochem

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Background: Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are members of the transforming growth factor beta (TGF-β) superfamily. Through autocrine and paracrine mechanisms, these two factors can regulate cell differentiation, proliferation, and other functions in the ovary locally. Furthermore, GDF9 and BMP15 play vital roles in follicular growth, atresia, ovulation, fertilization, reproduction, and maintenance. Numerous studies have demonstrated a synergy between BMP15 and GDF9. Studies in humans and mice have indicated that the synergy between BMP15 and GDF9 is primarily mediated by the bone morphogenetic protein type II receptor (BMPR2). The BMP15/GDF9 heterodimer needs to bind to the BMPR2-ALK4/5/7-ALK6 receptor complex to activate the SMAD2/3 signaling pathway. However, it is not clear which genes mediate and regulate the effects of the BMP15/GDF9 proteins on bovine cumulus cells (CCs). Methods: Our earlier study showed that BMPR2 is a gene that is directly targeted and regulated by miR-375. Therefore, we designed and synthesized an miR-375 mimics/inhibitor and regulated BMPR2 expression in bovine CCs by the overexpression or inhibition of miR-375. After the overexpression or inhibition of miR-375, the apoptosis rate of bovine CCs was measured by flow cytometry; changes in critical gene expression were measured by RT-qPCR and western blot assays; and the proliferation of bovine CCs was measured by CCK-8 assay. Results: In bovine CCs, the overexpression of miR-375 resulted in decreased BMPR2 and ALK7 expression, whereas the inhibition of miR-375 caused increased BMPR2 and ALK7 expression. The overexpression of miR-375 attenuated the proliferation ability and significantly increased the apoptosis rate of bovine CCs, whereas the inhibition of miR-375 did not significantly change the proliferation ability or apoptosis rate. Conclusions: BMPR2, a target of miR-375, is regulated by this molecule, thereby affecting expression of BMP15/GDF9 receptors, and the proliferation and apoptosis of bovine CCs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Regulatory Role of miRNA-375 in Expression of BMP15/GDF9 Receptors and its Effect on Proliferation and Apoptosis of Bovine Cumulus Cells

Chen

Liu

Jiang

et al. 2017

Cell Physiol Biochem

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“…Moreover, miR-375 is significantly downregulated in several types of tumors, and suppresses their proliferation by targeting some important genes, e.g., JAK2 , YAP1 , and PDK1 (Ding et al., 2010, Zhang et al., 2013, Zhou et al., 2014). Research has shown that miR-375 is a negative regulator of adipogenic differentiation by targeting bone morphogenetic protein receptor 2 (BMPR2) (Liu et al., 2016a). Osteoblastic and adipocytic lineages have alternative fates during development and aging, and increased adipogenesis correlates with decreased osteogenesis (Takada et al., 2009, Verma et al., 2002), which led us to speculate that miR-375 might play a role in the differentiation of stem cells toward osteogenic lineage.…”

Section: Introductionmentioning

confidence: 99%

Promotion Effects of miR-375 on the Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells

et al. 2017

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SummaryMicroRNA plays an important role in bone tissue engineering; however, its role and function in osteogenic differentiation warrant further investigation. In this study, we demonstrated that miR-375 was upregulated during the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASCs). Overexpression of miR-375 significantly enhanced hASCs osteogenesis both in vitro and in vivo, while knockdown of miR-375 inhibited the osteogenic differentiation of hASCs. Mechanistically, microarray analysis revealed DEPTOR as a target of miR-375 in hASCs. Knockdown of DEPTOR accelerated the osteogenic differentiation of hASCs by inhibiting AKT signaling, which mimics miR-375 overexpression. Furthermore, we confirmed that miR-375 regulated osteogenesis by targeting YAP1, and that YAP1 reversely bound to miR-375 promoter to inhibit miR-375 expression. Taken together, our results suggested that miR-375 promoted the osteogenic differentiation of hASCs via the YAP1/DEPTOR/AKT regulatory network, indicating that miR-375-targeted therapy might be a valuable approach to promote bone regeneration.

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“…Id1, Id2 , and Id3 regulate HC formation during development by negatively regulating Atoh1 (Ozeki et al, 2005; Jones et al, 2006; Laine et al, 2010; Zhan et al, 2017). Tfdp1 encodes a TF that binds to the promoter regions of a number of genes whose products are involved in cell cycle regulation or in tumor proliferation (Vairapandi et al, 2002; Yasui et al, 2003; Liu S. et al, 2016; Lu et al, 2016). Bmpr2 encodes a member of the bone morphogenetic protein receptor family of transmembrane serine/threonine kinases that play important roles in stem cell differentiation (Zeng et al, 2012; Larabee et al, 2015; Ramos-Solano et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Lgr5+ Progenitor Cell Transcriptomes after Neomycin Injury in the Neonatal Mouse Cochlea

Zhang

Yu³

et al. 2017

Front. Mol. Neurosci.

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Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea. Both in vitro and in vivo studies have shown that HC injury can spontaneously activate Lgr5+ progenitors to regenerate HCs in the neonatal mouse cochlea. Promoting HC regeneration requires the understanding of the mechanism of HC regeneration, and this requires knowledge of the key genes involved in HC injury-induced self-repair responses that promote the proliferation and differentiation of Lgr5+ progenitors. Here, as expected, we found that neomycin-treated Lgr5+ progenitors (NLPs) had significantly greater HC regeneration ability, and greater but not significant proliferation ability compared to untreated Lgr5+ progenitors (ULPs) in response to neomycin exposure. Next, we used RNA-seq analysis to determine the differences in the gene-expression profiles between the transcriptomes of NLPs and ULPs from the neonatal mouse cochlea. We first analyzed the genes that were enriched and differentially expressed in NLPs and ULPs and then analyzed the cell cycle genes, the transcription factors, and the signaling pathway genes that might regulate the proliferation and differentiation of Lgr5+ progenitors. We found 9 cell cycle genes, 88 transcription factors, 8 microRNAs, and 16 cell-signaling pathway genes that were significantly upregulated or downregulated after neomycin injury in NLPs. Lastly, we constructed a protein-protein interaction network to show the interaction and connections of genes that are differentially expressed in NLPs and ULPs. This study has identified the genes that might regulate the proliferation and HC regeneration of Lgr5+ progenitors after neomycin injury, and investigations into the roles and mechanisms of these genes in the cochlea should be performed in the future to identify potential therapeutic targets for HC regeneration.

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miR‐375 negatively regulates porcine preadipocyte differentiation by targeting BMPR2

Cited by 32 publications

References 43 publications

Regulatory Role of miRNA-375 in Expression of BMP15/GDF9 Receptors and its Effect on Proliferation and Apoptosis of Bovine Cumulus Cells

Regulatory Role of miRNA-375 in Expression of BMP15/GDF9 Receptors and its Effect on Proliferation and Apoptosis of Bovine Cumulus Cells

Promotion Effects of miR-375 on the Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells

Characterization of Lgr5+ Progenitor Cell Transcriptomes after Neomycin Injury in the Neonatal Mouse Cochlea

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