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糖尿病动脉粥样硬化大鼠模型的 microRNA 谱分析。

MicroRNA profiling of diabetic atherosclerosis in a rat model.

机构信息

The First Department of General Surgery, The First People's Hospital of Yunnan Province, 157 JinBi Road, Kunming, 650032, Yunnan, People's Republic of China.

Medical Faculty, Kunming University of Science and Technology, Kunming, Yunnan, China.

出版信息

Eur J Med Res. 2018 Nov 3;23(1):55. doi: 10.1186/s40001-018-0354-5.

DOI:10.1186/s40001-018-0354-5
PMID:30390707
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6215356/
Abstract

OBJECTIVE

The incidence of diabetic atherosclerosis (DA) is increasing worldwide. The study aim was to identify differentially expressed microRNAs (DE-miRs) potentially associated with the initiation and/or progression of DA, thereby yielding new insights into this disease.

METHODS

Matched iliac artery tissue samples were isolated from 6 male rats with or without DA. The Affymetrix GeneChip microRNA 4.0 Array was used to detect miRs. Differential expression between atherosclerotic group and non-atherosclerotic group samples was analyzed using the Gene-Cloud of Biotechnology Information platform. Targetscan and miRanda were then used to predict targets of DE-miRs. Functions and pathways were identified for significantly enriched candidate target genes and a DE-miR functional regulatory network was assembled to identify DA-associated core target genes.

RESULTS

A total of nine DE-miRs (rno-miR-206-3p, rno-miR-133a-5p, rno-miR-133b-3p, rno-miR-133a-3p, rno-miR-325-5p, rno-miR-675-3p, rno-miR-411-5p, rno-miR-329-3p, and rno-miR-126a-3p) were identified, all of which were up-regulated and together predicted to target 3349 genes. The target genes were enriched in known functions and pathways related to lipid and glucose metabolism. The functional regulatory network indicated a modulatory pattern of these metabolic functions with DE-miRs. The miR-gene network suggested arpp19 and MDM4 as possible DA-related core target genes.

CONCLUSION

The present study identified DE-miRs and miRNA-gene networks enriched for lipid and glucose metabolic functions and pathways, and arpp19 and MDM4 as potential DA-related core target genes, suggesting DE-miRs and/or arpp19 and MDM4 could act as potential diagnostic markers or therapeutic targets for DA.

摘要

目的

糖尿病动脉粥样硬化(DA)的发病率在全球范围内呈上升趋势。本研究旨在鉴定与 DA 的发生和/或进展相关的差异表达 microRNAs(DE-miRs),从而为该疾病提供新的见解。

方法

从 6 只雄性大鼠的髂动脉组织中分离出有或无 DA 的匹配组织样本。使用 Affymetrix GeneChip miRNA 4.0 阵列检测 miR。使用生物技术信息平台的 Gene-Cloud 分析粥样硬化组和非粥样硬化组样本之间的差异表达。然后使用 Targetscan 和 miRanda 预测 DE-miR 的靶标。对显著富集的候选靶基因进行功能和通路分析,并构建 DE-miR 功能调控网络,以鉴定与 DA 相关的核心靶基因。

结果

共鉴定出 9 个 DE-miRs(rno-miR-206-3p、rno-miR-133a-5p、rno-miR-133b-3p、rno-miR-133a-3p、rno-miR-325-5p、rno-miR-675-3p、rno-miR-411-5p、rno-miR-329-3p 和 rno-miR-126a-3p),均上调,共同预测靶向 3349 个基因。靶基因富集在与脂质和葡萄糖代谢相关的已知功能和通路中。功能调控网络表明,这些代谢功能与 DE-miRs 具有调节模式。miR-基因网络提示 arpp19 和 MDM4 可能是与 DA 相关的核心靶基因。

结论

本研究鉴定了富含脂质和葡萄糖代谢功能和通路的 DE-miRs 和 miRNA-基因网络,以及 arpp19 和 MDM4 作为潜在的 DA 相关核心靶基因,表明 DE-miRs 和/或 arpp19 和 MDM4 可能作为潜在的诊断标志物或治疗靶点用于 DA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/28a1b7891c82/40001_2018_354_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/9909138dc1cf/40001_2018_354_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/4aa3e431317f/40001_2018_354_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/b4125c7a7f1b/40001_2018_354_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/d3a0d8f6c013/40001_2018_354_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/b27e1da5a05f/40001_2018_354_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/31658d882e44/40001_2018_354_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/28a1b7891c82/40001_2018_354_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/9909138dc1cf/40001_2018_354_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/4aa3e431317f/40001_2018_354_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/b4125c7a7f1b/40001_2018_354_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/d3a0d8f6c013/40001_2018_354_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/b27e1da5a05f/40001_2018_354_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/31658d882e44/40001_2018_354_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f82c/6215356/28a1b7891c82/40001_2018_354_Fig7_HTML.jpg

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