Genetic Analysis Reveals Key Regulatory Axis in Aortic Dissection:CBL Regulated by HOXB13 and microRNA-1321  

作　　者：Zhiteng Chen Qingyuan Gao Junxiong Qiu Miaomiao Ge Shaohua Wang Cheng Liu Maoxiong Wu Wanbing He Jingfeng Wang Yangxin Chen Haifeng Zhang 

机构地区：[1]Department of Cardiology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,P.R.China [2]Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province,Guangdong 510120,P.R.China [3]Department of Cardiovascular Surgery,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,P.R.China [4]Department of Cardiology,Guangzhou First People’s Hospital,South China University of Technology,Guangzhou,Guangdong 510120,P.R.China

出　　处：《Cardiovascular Innovations and Applications》2024年第1期594-609,共16页心血管创新与应用(英文)

基　　金：supported by grants from the Guangzhou Basic and Applied Basic Research Foundation(202201010940);National Natural Science Foundation of China(82200306);Guangdong Basic and Applied Basic Research Foundation(2021A1515111092).

摘　　要：Background:Aortic dissection(AD)is a fatal cardiovascular disease for which the key involved genes are largely unknown.Here,we aimed to identify promising AD biomarkers from high-throughput RNA expressing data.Methods:In the GSE98770 dataset,differentially expressed mRNAs(DE-mRNAs)and microRNAs(DE-microRNAs)were identified through differentially expressed gene analysis and gene set enrichment analysis.The regulatory network between DE-mRNAs and DE-microRNAs was established,and hub genes were identified with Cytoscape.Relationships between hub genes and AD were confirmed in the Comparative Toxicogenomics Database(CTD).Potential key transcription factors were discovered with Cytoscape.Hub gene verification was performed by qPCR and immunofluorescence analyses of human specimens.Results:DE-mRNAs and DE-microRNAs were identified.Four mRNAs and microRNA-1321(miR-1321)were found to have the most connections with other genes.CBL was connected to the most genes and interacted with miR-1321,which was also connected to the most genes among the DE-microRNAs.In addition,CBL was associated with AD in the CTD.Among the top five transcription factors potentially regulating CBL transcription,only HOXB13 was a DE-mRNA.The findings were further successfully verified in human specimens.Conclusion:CBL,which may be transcriptionally regulated by HOXB13 and post-transcriptionally regulated by miR-1321,was identified as the most promising potential biomarker for AD.

关 键 词：aortic dissection bioinformatics analysis abstract homeobox b13 Cbl proto-oncogene microRNA-1321 

分 类 号：R543.1[医药卫生—心血管疾病]