Integrative Analysis of miRNA and mRNA Expression Profiles Associated With Human Atrial Aging.
Integrative Analysis of miRNA and mRNA Expression Profiles Associated With Human Atrial Aging.
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与人类心房衰老相关的 miRNA 和 mRNA 表达谱的综合分析。
DOI：
10.3389/fphys.2019.01226
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发表时间：
2019
影响因子：
4
通讯作者：
Zhihui Zhang
中科院分区：
文献类型：
--
作者：
Yan Yao;Chenxi Jiang;Fan Wang;Han Yan;De-Yong Long;Jing-Hua Zhao;Jiangang Wang;Chun-Xiao Zhang;Yang Li;Xiao-Li Tian;Qing Kenneth Wang;Gang Wu;Zhihui Zhang
背景系统研究老年人心房miRNA和mRNAs表达谱的研究成果有限。在这项研究中，我们的目标是确定miRNAs、基因和miRNA-mRNA相互作用网络与人类心房老化(AA)的关系。方法对12例主动脉瓣置换术患者的右心耳进行miRNA-seq和RNA-seq检查。所有患者均为窦性心律(SR)，按年龄分为4组。差异表达分析用于鉴定人再生障碍性贫血的miRNAs和基因。通过Pearson相关分析和miRNA靶标预测程序鉴定了人AA的miRNA-mRNA相互作用。结果7个miRNAs(4个上调和3个下调)和42个基因(23个上调和19个下调)在老年人和年轻人的右房组织中差异表达。生物信息学分析确定了114对推测的miRNA-mRNA与AA的相互作用和四种类型的相关性。途径丰富分析发现有40多条重要途径，前三位分别是节律性过程(P=7.50×10-5，q=0.034)、肿瘤的衰老和自噬(P=9.0×10-5，q=0.034)和细胞因子生物合成过程的正调控(P=1.1×10-4，q=0.034)。结论本研究揭示了再生障碍性贫血新的miRNA-mRNA相互作用网络和信号通路，为研究人类再生障碍性贫血的发生发展提供了新的思路。这些miRNA-mRNA相互作用在人类AA或AA相关心血管疾病中的潜在意义还需要进一步的研究。
Background Limited findings have been reported to systematically study miRNA and mRNA expression profiles in aged human atria. In this study, we aimed to identify miRNAs, genes, and miRNA-mRNA interaction networks for human atrial aging (AA). Methods Right atrial appendages from twelve patients who received aortic valve replacement were subjected to miRNA-seq and RNA-seq. All the patients were in sinus rhythm (SR) and stratified by age into four groups. Differential expression analysis was carried out to identify miRNAs and genes for human AA. The miRNA-mRNA interactions for human AA were identified by Pearson correlation analysis and miRNA target prediction programs. Results Seven miRNAs (4 upregulation and 3 downregulation) and 42 genes (23 upregulation and 19 downregulation) were differentially expressed in human right atrial tissues between older samples and younger samples. Bioinformatic analysis identified 114 pairs of putative miRNA-mRNA interactions on AA and four types of correlation. Pathway enrichment analysis identified over 40 significant pathways and the top three pathways included rhythmic process (P = 7.5 × 10–5, Q = 0.034), senescence and autophagy in cancer (P = 9.0 × 10–5, Q = 0.034), and positive regulation of cytokine biosynthetic process (P = 1.1 × 10–4, Q = 0.034). Conclusion Our study revealed novel miRNA-mRNA interaction networks and signaling pathways for AA, providing novel insights into the development of human AA. Future studies are needed to investigate the potential significance of these miRNA-mRNA interactions in human AA or AA-related cardiovascular diseases.