先天性心脏病新生儿血浆circRNAs芯片数据的生物信息学分析  

Bioinformatics analysis of circRNAs microarray data in plasma of newborns with congenital heart disease

作　　者：潘秋亚 赵静 崔玥 张雯婷 恽琪 郑爱斌 姚圣连 张伟 陈云[2] 顾猛 PAN Qiuya;ZHAO Jing;CUI Yue;ZHANG Wenting;YUN Qi;ZHENG Aibin;YAO Shenglian;ZHANG Wei;CHEN Yun;GU Meng(Department of Pediatrics,Changzhou Children's Hospital,Changzhou,Jiangsu 213003,China;Department of Pediatrics,the Traditional Chinese Medicine Hospital of Gaoyou,Yangzhou,Jiangsu 225699,China)

机构地区：[1]常州市儿童医院儿科,江苏常州213003 [2]高邮市中医医院儿科,江苏扬州225699

出　　处：《检验医学与临床》2022年第15期2063-2067,共5页Laboratory Medicine and Clinic

基　　金：江苏省常州市卫生健康委员会重大科技项目(ZD202031)。

摘　　要：目的利用高通量检测技术探讨新生儿先天性心脏病(CHD)的发病机制。方法将CHD新生儿血清与正常健康新生儿血清各3份进行配对分析,用微阵列探针进行环状RNA(circRNAs)检测。结果共检测到1711个circRNAs,其中差异表达的circRNAs 375个,在CHD新生儿血清中表达上调的circRNAs 115个,下调的circRNAs 260个(FDR>2,P<0.05)。通过美国Arraystar公司的微小RNA(miRNA)结合位点预测软件,该研究对每个差异表达的circRNA预测5个高匹配值的miRNA结合位点,375个差异表达的circRNAs预测结合了1546个miRNAs对14个miRNAs的靶基因进行信号通路分析,其中富集总分位于前3位的通路局灶性黏连、肌动蛋白细胞骨架调节、血管平滑肌收缩均与CHD的病理相关。通过hsa_circ_091419/miR-145/mRNA的网络图构建,该研究预测CHD相关的靶基因其34个,包括hsa-miR-145-3p的靶基因ITGB8。结论CHD的发病机制可能与circRNA和miRNA的上调或下调及circRNA-miRNA的共表达密切相关,具体涉及多种途径和多种细胞分子生物学过程的调控。Objective To explore the pathogenesis of neuborns with congenital heart disease(CHD)by high-throughput detection technology.Methods In this study,the serum of CHD newborns(n=3)was paired with that of healthy newborns(n=3).circular RNA(circRNAs)were detected by microarray probe.Results A total of 1711 circRNAs were found,among which 375 were differentially expressed.115 were up-regulated and 260 were down-regulated in CHD group(FDR>2,P<0.05).By using the microRNA(miRNA)binding site prediction software of Arraystar company,five miRNA binding sites with high matching value for each differentially expressed circRNA were predicted.The prediction of 375 differentially expressed circRNAs combined 1546 miRNAs.The target genes of 14 miRNAs were analyzed for signal pathways.Among them,the pathways with the top three enriched total scores were focal adhesion,actin cytoskeleton regulation and vascular smooth muscle contraction,which were all related to the pathology of CHD.Through hsa_circ_091419/mir-145/mRNA network construction,the study predicted 34 CHD related target genes,including the target gene ITGB8 of hsa-miR-145-3p.Conclusion The pathogenesis of CHD may be closely related to the up-regulation or down-regulation of circRNA and miRNA or the co-expression of cirRNA-miRNA,which involves the regulation of multiple pathways and cellular and molecular biological processes.

关 键 词：circRNAs 先天性心脏病 GO分析 信号通路 circRNA/miRNA/mRNA网络 

分 类 号：R446.9[医药卫生—诊断学]