Effect of MiR‐100‐5p on proliferation and apoptosis of goat endometrial stromal cell in vitro and embryo implantation in vivo

Ma, Li; Zhang, Meng; Cao, Fangjun; Han, Jincheng; Han, Peng; Wu, Yeting; Deng, Renyi; Zhang, Guanghui; An, Xiaopeng; Zhang, Lei; Song, Yuxuan; Cao, Binyun

doi:10.1111/jcmm.17226

Cited by 11 publications

(7 citation statements)

References 36 publications

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“…β-catenin plays a crucial role in endometrium functions and is considered an imperative signal in invasion and differentiation of trophoblasts and embryo implantation [39,52]. Moreover, Endo-EVs cargo contained miR-100, which is expressed in human endometrial cell-derived EVs and activates focal adhesion kinase (FAK) and c-Jun N-terminal kinase (JNK) and promotes the invasion and migration of human and goat trophoblasts [12,53,54]. Furthermore, Endo-EVs contained miR-132 that is expressed temporally in porcine endometrium at the time of embryo implantation [55] and is a potential factor for enhancing trophoblast invasion and embryo implantation by targeting death-associated protein kinase 1 (DAPK-1) [56].…”

Section: Discussionmentioning

confidence: 99%

ROCK Inhibitor (Y-27632) Abolishes the Negative Impacts of miR-155 in the Endometrium-Derived Extracellular Vesicles and Supports Embryo Attachment

Saadeldin

Tanga

Bang

et al. 2022

Cells

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Extracellular vesicles (EVs) are nanosized vesicles that act as snapshots of cellular components and mediate cellular communications, but they may contain cargo contents with undesired effects. We developed a model to improve the effects of endometrium-derived EVs (Endo-EVs) on the porcine embryo attachment in feeder-free culture conditions. Endo-EVs cargo contents were analyzed using conventional and real-time PCR for micro-RNAs, messenger RNAs, and proteomics. Porcine embryos were generated by parthenogenetic electric activation in feeder-free culture conditions supplemented with or without Endo-EVs. The cellular uptake of Endo-EVs was confirmed using the lipophilic dye PKH26. Endo-EVs cargo contained miR-100, miR-132, and miR-155, together with the mRNAs of porcine endogenous retrovirus (PERV) and β-catenin. Targeting PERV with CRISPR/Cas9 resulted in reduced expression of PERV mRNA transcripts and increased miR-155 in the Endo-EVs, and supplementing these in embryos reduced embryo attachment. Supplementing the medium containing Endo-EVs with miR-155 inhibitor significantly improved the embryo attachment with a few outgrowths, while supplementing with Rho-kinase inhibitor (RI, Y-27632) dramatically improved both embryo attachment and outgrowths. Moreover, the expression of miR-100, miR-132, and the mRNA transcripts of BCL2, zinc finger E-box-binding homeobox 1, β-catenin, interferon-γ, protein tyrosine phosphatase non-receptor type 1, PERV, and cyclin-dependent kinase 2 were all increased in embryos supplemented with Endo-EVs + RI compared to those in the control group. Endo-EVs + RI reduced apoptosis and increased the expression of OCT4 and CDX2 and the cell number of embryonic outgrowths. We examined the individual and combined effects of RI compared to those of the miR-155 mimic and found that RI can alleviate the negative effects of the miR-155 mimic on embryo attachment and outgrowths. EVs can improve embryo attachment and the unwanted effects of the de trop cargo contents (miR-155) can be alleviated through anti-apoptotic molecules such as the ROCK inhibitor.

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Section: Discussionmentioning

confidence: 99%

ROCK Inhibitor (Y-27632) Abolishes the Negative Impacts of miR-155 in the Endometrium-Derived Extracellular Vesicles and Supports Embryo Attachment

Saadeldin

Tanga

Bang

et al. 2022

Cells

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“…To determine the miRNA(s) from ADSC-Exos which can stimulate EpSC proliferation, we searched the literature to find out which miRNA among the top 5 miRNAs in ADSC-Exos could promote cell proliferation. Among these miRNAs, miR-127 and Let-7b have inhibitory effect on cell proliferation [29][30][31]; miR-92a, miR-222-3p, and miR-100-5p have been reported to stimulate or inhibit cell proliferation [22][23][24][25][26][32][33][34][35]. We then examined the effect of miR-92a-3p, miR-222-3p, and miR-100-5p on the proliferation of human EpSCs.…”

Section: Stem Cells Internationalmentioning

confidence: 99%

“…miR-100-5p is one of the most abundant miR-NAs in ADSC-Exos. It has been reported to promote or inhibit the proliferation of cells from different origin by targeting different molecules [22][23][24][25][26]. miR-100-5p promoted the proliferation of human placental microvascular endothelial cells by targeting homeodomain-interacting protein kinase 2 to activate the PI3K/AKT pathway [24].…”

Section: Introductionmentioning

confidence: 99%

“…miR-100-5p promoted the proliferation of human placental microvascular endothelial cells by targeting homeodomain-interacting protein kinase 2 to activate the PI3K/AKT pathway [ 24 ]. miR-100-5p inhibited endometrial stromal cell proliferation by targeting HOXA1 to inhibit the PI3K/AKT and ERK pathways [ 26 ]. As miR-100-5p from umbilical cord mesenchymal stem cell-derived exosomes can accelerate vaginal epithelial cell proliferation [ 22 ], we proposed that miR-100-5p from ADSC-Exos might have proproliferative effect on EpSCs.…”

Section: Introductionmentioning

confidence: 99%

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miR-100-5p Promotes Epidermal Stem Cell Proliferation through Targeting MTMR3 to Activate PIP3/AKT and ERK Signaling Pathways

Liu

Yang

et al. 2022

Stem Cells International

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Skin epidermal stem cells (EpSCs) play a critical role in wound healing and are ideal seed cells for skin tissue engineering. Exosomes from human adipose-derived stem cells (ADSC-Exos) promote human EpSC proliferation, but the underlying mechanism remains unclear. Here, we investigated the effect of miR-100-5p, one of the most abundant miRNAs in ADSC-Exos, on the proliferation of human EpSCs and explored the mechanisms involved. MTT and BrdU incorporation assays showed that miR-100-5p mimic transfection promoted EpSC proliferation in a time-dependent manner. Cell cycle analysis showed that miR-100-5p mimic transfection significantly decreased the percentage of cells in the G1 phase and increased the percentage of cells in the G2/M phase. Myotubularin-related protein 3 (MTMR3), a lipid phosphatase, was identified as a direct target of miR-100-5p. Knockdown of MTMR3 in EpSCs by RNA interference significantly enhanced cell proliferation, decreased the percentage of cells in the G1 phase and increased the percentage of cells in the S phase. Overexpression of MTMR3 reversed the proproliferative effect of miR-100-5p on EpSCs, indicating that miR-100-5p promoted EpSC proliferation by downregulating MTMR3. Mechanistic studies showed that transfection of EpSCs with miR-100-5p mimics elevated the intracellular PIP3 level, induced AKT and ERK phosphorylation, and upregulated cyclin D1, E1, and A2 expression, which could be attenuated by MTMR3 overexpression. Consistently, intradermal injection of ADSC-Exos or miR-100-5p-enriched ADSC-Exos into cultured human skin tissues significantly reduced MTMR3 expression and increased the thickness of the epidermis and the number of EpSCs in the basal layer of the epidermis. The aforementioned effect of miR-100-5p-enriched ADSC-Exos was stronger than that of ADSC-Exos and was reversed by MTMR3 overexpression. Collectively, our findings indicate that miR-100-5p promotes EpSC proliferation through MTMR3-mediated elevation of PIP3 and activation of AKT and ERK. miR-100-5p-enriched ADSC-Exos can be used to treat skin wound and expand EpSCs for generating epidermal autografts and engineered skin equivalents.

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“…Several potential regulatory factors for regulating mammalian reproduction have been researched in recent years, including noncoding RNAs (ncRNAs) (e.g., long noncoding RNAs, micro RNAs) ( Zhao et al, 2020 ; Ma et al, 2022 ). CircRNAs are a new type of regulatory ncRNA that have been rediscovered to regulate gene expression in eukaryote cells and are characterized by covalently closed-loop and splice connection sites formed by the covalent connection of the 3' and 5' ends ( Memczak et al, 2013 ; Liang and Wilusz, 2014 ; Wilusz, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of circular RNA profiles of oviduct reveal the potential mechanism in prolificacy trait of goat in the estrus cycle

et al. 2022

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The mammalian oviduct is functionally highly diverse during the estrus cycle. It provides a suitable milieu for oocyte maturation, sperm capacitation, fertilization, early embryo development and transportation. While there have been many studies of molecular mechanisms on the kidding number of goats, a systematic analysis by which the underlying circular RNAs (circRNAs) changes in the oviduct related to prolificacy traits is lacking. Herein, we present a comprehensive circRNA atlas of the oviduct among high-and low-fecundity goats in the follicular phase (FH vs. FL), luteal phase (LH vs. LL), and estrus cycle (FH vs. LH; FL vs. LL) to unravel their potential regulatory mechanisms in improving kidding number. We generated RNA sequencing data, and identified 4,078 circRNAs from twenty sampled Yunshang black goats. Many of these circRNAs are exon-derived and differentially expressed between each comparison group. Subsequently, eight differentially expressed (DE) circRNAs were validated by RT-qPCR, which was consistent with the RNA-seq data. GO and KEGG enrichment analyses suggested that numerous host genes of DE circRNAs were involved in the hormone secretion, gamete production, fertilization, and embryo development processes. The competing endogenous RNA (ceRNA) interaction network analysis revealed that 2,673 circRNA-miRNA-mRNA axes (including 15 DE circRNAs, 14 miRNAs, and 1,699 mRNAs) were formed, and several target genes derived from the ceRNA network were associated with oviduct functions and reproduction, including SMAD1, BMPR1B, IGF1, REV1, and BMP2K. Furthermore, might play important roles in reproduction. Finally, a novel circRNA, circIQCG, was identified as potentially involved in embryo development. Overall, our study provides a resource of circRNAs to understand the oviductal function and its connection to prolificacy trait of goats in the differentiation estrus cycle.

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Effect of MiR‐100‐5p on proliferation and apoptosis of goat endometrial stromal cell in vitro and embryo implantation in vivo

Cited by 11 publications

References 36 publications

ROCK Inhibitor (Y-27632) Abolishes the Negative Impacts of miR-155 in the Endometrium-Derived Extracellular Vesicles and Supports Embryo Attachment

ROCK Inhibitor (Y-27632) Abolishes the Negative Impacts of miR-155 in the Endometrium-Derived Extracellular Vesicles and Supports Embryo Attachment

miR-100-5p Promotes Epidermal Stem Cell Proliferation through Targeting MTMR3 to Activate PIP3/AKT and ERK Signaling Pathways

Characterization of circular RNA profiles of oviduct reveal the potential mechanism in prolificacy trait of goat in the estrus cycle

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