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长链非编码 RNA、微小 RNA 和 mRNAs 相关 ceRNA 网络在支气管肺发育不良新生鼠模型中的综合分析。

Integrative analysis of lncRNAs, miRNAs, and mRNAs-associated ceRNA network in a neonatal mouse model of bronchopulmonary dysplasia.

机构信息

Department of Pediatrics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

出版信息

J Matern Fetal Neonatal Med. 2021 Oct;34(19):3234-3245. doi: 10.1080/14767058.2020.1815700. Epub 2020 Sep 13.


DOI:10.1080/14767058.2020.1815700
PMID:32924699
Abstract

OBJECTIVE: To elucidate the potential roles of the lncRNA-mediated competitive endogenous RNA (ceRNA) network in the pathogenesis of bronchopulmonary dysplasia (BPD), we performed an integrated bioinformatics analysis based on miRNA and mRNA microarray datasets between BPD and normal samples. STUDY DESIGN: The mRNA and miRNA expression profiles of BPD were downloaded from the Gene Expression Omnibus (GEO) database to perform an integrated analysis. The limma package was used to identify differentially expressed genes (DEGs) and differentially expressed miRNA (DEmiRs), followed by functional enrichment analysis of DEGs. DEmiR-DEG and DEmiRNA-lncRNA interactions were predicted. Subsequently, the lncRNA-related ceRNA network was structured. Finally, a newborn BPD mouse model was established, and quantitative real-time PCR (qPCR) was used to validate the expression of the selected mRNAs, miRNAs, and lncRNAs. RESULTS: A total of 445 DEGs and 155 DEmiRs were obtained by comparing BPD samples and normal samples. Functional enrichment analysis showed that DEGs were primarily enriched in GO terms such as cell division and inflammatory response; and DEGs were mainly involved in the p53 signaling pathway. The --roundabout guidance receptor 2 () and --BMP/retinoic acid-inducible neural specific 1 () ceRNA axes were obtained by constructing the ceRNA network. In addition, the upregulation of and while the downregulation of ; as well as the upregulation of and but the downregulation of were validated by qPCR. CONCLUSION: The -- and -- axes may serve important role in the development of BPD. These findings might provide novel insight for a comprehensive understanding of molecular mechanisms in BPD, and genes in the ceRNA network might be considered as potential biomarkers and therapeutic targets against BPD.

摘要

目的:通过整合 miRNA 和 mRNA 微阵列数据集,对支气管肺发育不良(BPD)中长链非编码 RNA(lncRNA)介导的竞争性内源 RNA(ceRNA)网络的潜在作用进行研究,我们进行了一项基于 miRNA 和 mRNA 微阵列数据集的综合生物信息学分析。

研究设计:从基因表达综合数据库(GEO)数据库下载 BPD 的 mRNA 和 miRNA 表达谱,进行综合分析。使用 limma 包识别差异表达基因(DEGs)和差异表达 miRNA(DEmiRs),然后对 DEGs 进行功能富集分析。预测 DEmiR-DEG 和 DEmiRNA-lncRNA 相互作用。随后,构建 lncRNA 相关的 ceRNA 网络。最后,建立新生 BPD 小鼠模型,采用实时定量 PCR(qPCR)验证所选 mRNAs、miRNAs 和 lncRNAs 的表达。

结果:通过比较 BPD 样本和正常样本,获得了 445 个 DEGs 和 155 个 DEmiRs。功能富集分析显示,DEGs 主要富集于细胞分裂和炎症反应等 GO 术语;DEGs 主要参与 p53 信号通路。通过构建 ceRNA 网络,获得了 --roundabout 制导受体 2()和 --BMP/视黄酸诱导的神经特异 1()ceRNA 轴。此外,qPCR 验证了 -- 和 -- 轴的上调,而 -- 及其下游靶基因的下调;以及 -- 和 -- 的上调,但 -- 的下调。

结论:-- 和 -- 轴可能在 BPD 的发展中发挥重要作用。这些发现可能为全面了解 BPD 的分子机制提供新的见解,ceRNA 网络中的基因可能被视为 BPD 的潜在生物标志物和治疗靶点。

相似文献

[1]
Integrative analysis of lncRNAs, miRNAs, and mRNAs-associated ceRNA network in a neonatal mouse model of bronchopulmonary dysplasia.

J Matern Fetal Neonatal Med. 2021-10

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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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J Periodontal Res. 2018-3-8

引用本文的文献

[1]
Decoding bronchopulmonary dysplasia in premature infants through an epigenetic lens.

Front Med (Lausanne). 2025-4-3

[2]
Pathogenesis of Bronchopulmonary Dysplasia: Role of Oxidative Stress from 'Omics' Studies.

Antioxidants (Basel). 2022-12-1

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