Integrative analysis of miRNA-mRNA network in high altitude retinopathy by bioinformatics analysis.
Integrative analysis of miRNA-mRNA network in high altitude retinopathy by bioinformatics analysis.
复制标题
高原视网膜病变中miRNA-mRNA网络的生物信息学综合分析
DOI：
10.1042/bsr20200776
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发表时间：
2021-01-29
影响因子：
4
通讯作者：
Qiu Q
中科院分区：
文献类型：
--
作者：
Su T;Gu C;Draga D;Zhou C;Lhamo T;Zheng Z;Qiu Q
高原视网膜病变（high -altitude retinopathy， HAR）是急性缺氧在高海拔地区的眼部表现。虽然近年来许多研究揭示了HAR的病理生理，但其分子机制尚不清楚。我们的研究旨在通过综合生物信息学分析系统地鉴定HAR的基因和microRNA (miRNA)，并探索与HAR相关的潜在生物标志物。mRNA和miRNA的表达谱来自基因表达综合数据库。我们进行了基因本体功能注释和京都基因与基因组百科全书通路分析。进行潜在靶基因分析和miRNA-mRNA网络分析。采用定量RT-PCR （qRT-PCR）对生物信息学分析结果进行验证。通过一系列的生物信息学分析和实验，我们选择了16个差异表达mirna （de - mirna）和157个与急性高山病（AMS）相关的差异表达基因，构建了包含240对关系对的miRNA-mRNA网络。从蛋白-蛋白相互作用网络中筛选出枢纽基因：IL7R、FOS、IL10、FCGR2A、DDX3X、CDK1、BCL11B和HNRNPH1，这些基因在AMS组均下调。然后，在我们的缺氧诱导的HAR细胞模型中，通过qRT-PCR验证了9个上调的de - mirna和8个枢纽基因。miR-3177-3p、miR-369-3p、miR-603、miR-495、miR-4791、miR-424-5p、FOS、IL10和IL7R的表达与我们的生物信息学结果一致。综上所述，FOS、IL10、IL-7R和7种de - mirna可能参与了HAR的发展。我们的研究结果将有助于识别生物标志物，促进未来HAR的有效预防和治疗。
Abstract High-altitude retinopathy (HAR) is an ocular manifestation of acute oxygen deficiency at high altitudes. Although the pathophysiology of HAR has been revealed by many studies in recent years, the molecular mechanism is not yet clear. Our study aimed to systematically identify the genes and microRNA (miRNA) and explore the potential biomarkers associated with HAR by integrated bioinformatics analysis. The mRNA and miRNA expression profiles were obtained from the Gene Expression Omnibus database. We performed Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Potential target gene analysis and miRNA–mRNA network analysis were also conducted. Quantitative RT-PCR (qRT-PCR) was used to validate the results of the bioinformatics analysis. Through a series of bioinformatics analyses and experiments, we selected 16 differentially expressed miRNAs (DE-miRNAs) and 157 differentially expressed genes related to acute mountain sickness (AMS) and constructed a miRNA–mRNA network containing 240 relationship pairs. The hub genes were filtered from the protein-protein interaction network: IL7R, FOS, IL10, FCGR2A, DDX3X, CDK1, BCL11B and HNRNPH1, which were all down-regulated in the AMS group. Then, nine up-regulated DE-miRNAs and eight hub genes were verified by qRT-PCR in our hypoxia-induced HAR cell model. The expression of miR-3177-3p, miR-369-3p, miR-603, miR-495, miR-4791, miR-424-5p, FOS, IL10 and IL7R was consistent with our bioinformatics results. In conclusion, FOS, IL10, IL-7R and 7 DE-miRNAs may participate in the development of HAR. Our findings will contribute to the identification of biomarkers and promote the effective prevention and treatment of HAR in the future.