Comprehensive analysis of circRNA-miRNA-mRNA network related to angiogenesis in recurrent implantation failure.

IF 2.1 4区医学 Q3 GENETICS & HEREDITY

BMC Medical Genomics Pub Date : 2024-07-30 DOI:10.1186/s12920-024-01944-1

Anran Wang, Piaopiao Chen

{"title":"Comprehensive analysis of circRNA-miRNA-mRNA network related to angiogenesis in recurrent implantation failure.","authors":"Anran Wang, Piaopiao Chen","doi":"10.1186/s12920-024-01944-1","DOIUrl":null,"url":null,"abstract":"Background: Abnormal endometrial blood flow causes a decrease in endometrial receptivity and is considered a relatively independent risk factor for recurrent implantation failure (RIF). This study aimed to explore the potentially functional circRNA-miRNA-mRNA network in RIF, and further explore its mechanism.Methods: Datasets were downloaded from the GEO database to identify differentially expressed circRNAs, miRNAs and mRNAs. The circRNA-miRNA-mRNA and PPI networks were constructed using Cytoscape 3.6.0 and the STRING database, the hub genes were identified with the cytoHubba plug-in, and a circRNA-miRNA-hub mRNA regulatory sub-network was constructed. Then, GO and KEGG pathway enrichment analyses of the hub genes were performed to comprehensively analyze the mechanism of hub mRNAs in RIF. Due to the results of circRNAs-miRNAs-hub mRNAs regulatory network, we verified the expression of circRNA_0001721, circRNA_0000714, miR-17-5p, miR-29b-3p, HIF1A and VEGFA in the RIF mouse model by qRT‒PCR and western blotting.Results: We initially identified 175 DEmRNAs, 48 DEmiRNAs and 56 DEcircRNAs in RIF associated with angiogenesis and constructed a circRNA-miRNA‒mRNA network and PPI network. We further identified six hub genes in the acquired network. Based on these genes, functional enrichment analysis revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. In addition, the interaction networks of circRNA_0001721/miR-17-5p/HIF1A and the circRNA_0000714/miR-29b-3p/VEGFA axis were predicted. In the RIF mouse model, circRNA_0001721, circRNA_0000714, HIF1A and VEGFA were down-regulated, whereas miR-17-5p and miR-29b-3p were up-regulated according to qRT‒PCR and western blotting.Conclusion: This study revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. The circRNA_0001721/miR-17-5p/HIF1A and circRNA_0000714/miR-29b-3p/VEGFA axes might play a role in the pathogenesis of endometrial angiogenesis in RIF.","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"193"},"PeriodicalIF":2.1000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290139/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medical Genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12920-024-01944-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Abnormal endometrial blood flow causes a decrease in endometrial receptivity and is considered a relatively independent risk factor for recurrent implantation failure (RIF). This study aimed to explore the potentially functional circRNA-miRNA-mRNA network in RIF, and further explore its mechanism.

Methods: Datasets were downloaded from the GEO database to identify differentially expressed circRNAs, miRNAs and mRNAs. The circRNA-miRNA-mRNA and PPI networks were constructed using Cytoscape 3.6.0 and the STRING database, the hub genes were identified with the cytoHubba plug-in, and a circRNA-miRNA-hub mRNA regulatory sub-network was constructed. Then, GO and KEGG pathway enrichment analyses of the hub genes were performed to comprehensively analyze the mechanism of hub mRNAs in RIF. Due to the results of circRNAs-miRNAs-hub mRNAs regulatory network, we verified the expression of circRNA_0001721, circRNA_0000714, miR-17-5p, miR-29b-3p, HIF1A and VEGFA in the RIF mouse model by qRT‒PCR and western blotting.

Results: We initially identified 175 DEmRNAs, 48 DEmiRNAs and 56 DEcircRNAs in RIF associated with angiogenesis and constructed a circRNA-miRNA‒mRNA network and PPI network. We further identified six hub genes in the acquired network. Based on these genes, functional enrichment analysis revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. In addition, the interaction networks of circRNA_0001721/miR-17-5p/HIF1A and the circRNA_0000714/miR-29b-3p/VEGFA axis were predicted. In the RIF mouse model, circRNA_0001721, circRNA_0000714, HIF1A and VEGFA were down-regulated, whereas miR-17-5p and miR-29b-3p were up-regulated according to qRT‒PCR and western blotting.

Conclusion: This study revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. The circRNA_0001721/miR-17-5p/HIF1A and circRNA_0000714/miR-29b-3p/VEGFA axes might play a role in the pathogenesis of endometrial angiogenesis in RIF.

查看原文本刊更多论文

全面分析复发性植入失败中与血管生成相关的 circRNA-miRNA-mRNA 网络。

背景：子宫内膜血流异常会导致子宫内膜接受能力下降，被认为是导致反复种植失败（RIF）的一个相对独立的危险因素。本研究旨在探索RIF中潜在的功能性circRNA-miRNA-mRNA网络，并进一步探讨其机制：方法：从 GEO 数据库下载数据集，识别差异表达的 circRNA、miRNA 和 mRNA。利用Cytoscape 3.6.0和STRING数据库构建circRNA-miRNA-mRNA和PPI网络，利用cytoHubba插件识别中枢基因，构建circRNA-miRNA-中枢mRNA调控子网络。然后，对中枢基因进行了GO和KEGG通路富集分析，以全面分析中枢mRNA在RIF中的作用机制。根据circRNAs-miRNAs-hub mRNAs调控网络的结果，我们通过qRT-PCR和Western blotting验证了circRNA_0001721、circRNA_0000714、miR-17-5p、miR-29b-3p、HIF1A和VEGFA在RIF小鼠模型中的表达：结果：我们初步鉴定了 RIF 中与血管生成相关的 175 个 DEmRNA、48 个 DEmiRNA 和 56 个 DEcircRNA，并构建了 circRNA-miRNA-mRNA 网络和 PPI 网络。我们还在获得的网络中发现了六个中心基因。基于这些基因的功能富集分析表明，HIF-1 信号通路在 RIF 的子宫内膜血管生成中起着至关重要的作用。此外，还预测了circRNA_0001721/miR-17-5p/HIF1A和circRNA_0000714/miR-29b-3p/VEGFA轴的相互作用网络。在 RIF 小鼠模型中，根据 qRT-PCR 和 Western 印迹，circRNA_0001721、circRNA_0000714、HIF1A 和 VEGFA 下调，而 miR-17-5p 和 miR-29b-3p 上调：结论：本研究揭示了HIF-1信号通路在RIF子宫内膜血管生成中的重要作用。circRNA_0001721/miR-17-5p/HIF1A和circRNA_0000714/miR-29b-3p/VEGFA轴可能在RIF子宫内膜血管生成的发病机制中发挥作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

BMC Medical Genomics 医学-遗传学

CiteScore

3.90

自引率

0.00%

发文量

243

审稿时长

3.5 months

期刊介绍： BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.