基于miRNA-mRNA调控网络分析并验证易损斑块形成的潜在分子机制  

Analysis and validation of potential molecular mechanisms of vulnerable plaque formation based on miRNA-mRNA regulatory network

作　　者：张晓璐 葛为勇 曾文赟 于群 王一婧[5] 姜希娟 ZHANG Xiao-lu;GE Wei-yong;ZENG Wen-yun;YU Qun;WANG Yi-jing;JIANG Xi-juan(School of Integrative Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学中西医结合学院,天津301617 [2]滨海慢性病防控与健康创新研究院,天津300461 [3]赣州市人民医院肿瘤科,江西赣州341000 [4]遵义医科大学基础医学院,贵州遵义563000 [5]天津中医药大学护理学院,天津301617

出　　处：《广东医学》2024年第7期824-831,共8页Guangdong Medical Journal

基　　金：国家自然科学基金(82074211);天津中医药大学中西医结合学院2019年度研究生创新基金(ZXYCXLX201902)。

摘　　要：目的分析并验证易损动脉粥样硬化(atherosclerosis,AS)斑块形成的潜在分子机制。方法通过形态学染色验证主动脉根和头臂干中是否存在AS斑块。采用GSE34646和GSE34647数据集中的差异表达miRNA(differentially expressed miRNAs,DEMs)分析并预测DEMs靶基因(DEMs-target genes,DEMs-TGs)。其次,筛选GSE10000数据集易损斑块中差异表达基因(differentially expressed genes in advanced plaque,DEGs-AP)。然后将DEGs-AP与DEMs-TG进行交集,以筛选候选基因。对获得的基因构建PPI网络,并鉴定关键基因。接着建立miRNA-mRNA调控网络,并使用受试者工作特征(ROS)曲线评估关键基因的预后。最后采用RT-qPCR检测主动脉中预测的mRNA和miRNA水平。结果组织病理学检查显示,模型组有明显的易损斑块。通过GSE34646和GSE34647数据集筛选,在易损斑块中获得44个DEM,并预测得到3171个和8075个miRNA靶基因。在GSE10000数据集中,获得了3441个DEGs-AP。然后将DEGs-AP和DEMs-TG交集,得到936个候选基因。PPI网络鉴定了10个上调和10个下调的枢纽基因,用于构建miRNA-mRNA调控网络。结论Let-7g-3p-ADAM10/PIK3R1/C3AR1可能是RT-qPCR预测和诊断晚期斑块的潜在miRNA-mRNA调控轴。Objective To analyze and validate the potential molecular mechanisms involved in the formation of vulnerable atherosclerosis plaques through the miRNA-mRNA regulatory network.Methods Morphological staining was used to validate the presence of atherosclerotic plaques in the aortic root and brachiocephalic trunk.Differentially expressed miRNAs(DEMs)from the GSE34646 and GSE34647 datasets were analyzed,and their target genes(DEMs-TGs)were predicted.Differentially expressed genes in advanced plaque(DEGs-AP)were then screened from the GSE10000 dataset.The intersection of DEGs-AP and DEMs-TGs was taken to identify candidate genes.A protein-protein interaction(PPI)network was constructed for the identified genes,and key genes were identified.An miRNA-mRNA regulatory network was established,and the prognostic value of key genes was assessed using receiver operating characteristic(ROC)curves.Finally,RT-qPCR was used to detect the predicted mRNA and miRNA levels in the aorta.Results Histopathological examination showed significant vulnerable plaques in the model group.Forty-four DEMs were identified in vulnerable plaques from the GSE34646 and GSE34647 datasets,predicting 3,171 and 8,075 miRNA target genes,respectively.The GSE10000 dataset identified 3,441 DEGs-AP.The intersection of DEGs-AP and DEMs-TGs yielded 936 candidate genes.The PPI network identified 10 upregulated and 10 downregulated hub genes,which were used to construct the miRNA-mRNA regulatory network.Conclusion Let-7g-3p-ADAM10/PIK3R1/C3AR1 may be the potential miRNA-mRNA regulatory axes for prognostication and diagnosis of advanced plaques by the RT-qPCR.

关 键 词：动脉粥样硬化 MIRNA 易损斑块 生物信息学 

分 类 号：R541.4[医药卫生—心血管疾病] R543.1[医药卫生—内科学]