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慢性间歇性低氧诱导的ApoE(-/-)小鼠白色脂肪组织损伤中微小RNA改变的综合分析

A comprehensive analysis of microRNA alteration in an ApoE(-/-) mice model of white adipose tissue injury induced by chronic intermittent hypoxia.

作者信息

Zhang Jinjie, Guo Yaopeng, Ji Meilin, Lin Shu, Liu Dexin, Chen Qingshi

机构信息

The Second Clinical Medical College, Fujian Medical University, Quanzhou, China.

The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

出版信息

Front Genet. 2025 Mar 26;16:1474223. doi: 10.3389/fgene.2025.1474223. eCollection 2025.

DOI:10.3389/fgene.2025.1474223
PMID:40206502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11979184/
Abstract

BACKGROUND

MicroRNAs (miRNAs) represent a class of noncoding small RNAs and are implicated in many diseases. However, the role of miRNA in obstructive sleep apnea (OSA)-induced white adipose tissue (WAT) dysfunction remains to be fully elucidated. Using miRNA sequencing (miRNA-seq), we uncovered the miRNA expression profiles in chronic intermittent hypoxia (CIH)-induced WAT dysfunction mice.

METHODS

We established an apolipoprotein-deficient (ApoE-/-) CIH mouse model and identified differentially expressed miRNAs (DEmiRs) using miRNA-seq technology. With the help of Gene Ontology (GO) functional enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we determined the biological functions of these DEmiRs. In addition, RT-qPCR was performed for further evaluation of the sequencing data. Finally, we constructed a conserved negative correlation (CNC) network to expound the relationship between miRNA and target genes.

RESULTS

Overall, 13 miRNAs were found to be upregulated and 18 miRNAs downregulated in the CIH-induced mouse model of WAT dysfunction. KEGG pathway analysis results indicated that the lysosome pathway participated in CIH-induced WAT dysfunction. Then, eight miRNAs were shortlisted for RT-qPCR validation. Based on the data, we chose these DEmiRs to construct a miRNA-mRNA regulatory network.

CONCLUSION

Overall, we identified 31 DEmiRs in the ApoE-/- CIH mouse model. Our findings may play a major role in explaining the pathophysiological mechanisms of WAT dysfunction induced by obstructive sleep apnea.

摘要

背景

微小RNA(miRNA)是一类非编码小RNA,与多种疾病相关。然而,miRNA在阻塞性睡眠呼吸暂停(OSA)诱导的白色脂肪组织(WAT)功能障碍中的作用仍有待充分阐明。通过miRNA测序(miRNA-seq),我们揭示了慢性间歇性缺氧(CIH)诱导的WAT功能障碍小鼠中的miRNA表达谱。

方法

我们建立了载脂蛋白缺陷(ApoE-/-)CIH小鼠模型,并使用miRNA-seq技术鉴定差异表达的miRNA(DEmiR)。借助基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路分析,我们确定了这些DEmiR的生物学功能。此外,进行了RT-qPCR以进一步评估测序数据。最后,我们构建了一个保守负相关(CNC)网络来阐述miRNA与靶基因之间的关系。

结果

总体而言,在CIH诱导的WAT功能障碍小鼠模型中,发现13种miRNA上调,18种miRNA下调。KEGG通路分析结果表明溶酶体通路参与了CIH诱导的WAT功能障碍。然后,挑选了8种miRNA进行RT-qPCR验证。基于这些数据,我们选择这些DEmiR构建了一个miRNA- mRNA调控网络。

结论

总体而言,我们在ApoE-/- CIH小鼠模型中鉴定出31种DEmiR。我们的发现可能在解释阻塞性睡眠呼吸暂停诱导的WAT功能障碍的病理生理机制中起主要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/ea5e0cde009c/fgene-16-1474223-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/bf117b27b8f1/fgene-16-1474223-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/ee554fd8f37a/fgene-16-1474223-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/3d7e45b3074e/fgene-16-1474223-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/15c2f638dacd/fgene-16-1474223-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/ea5e0cde009c/fgene-16-1474223-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/bf117b27b8f1/fgene-16-1474223-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/ee554fd8f37a/fgene-16-1474223-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/3d7e45b3074e/fgene-16-1474223-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/15c2f638dacd/fgene-16-1474223-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/11979184/ea5e0cde009c/fgene-16-1474223-g005.jpg

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