Differential expression profiles and functional analysis of long non-coding RNAs in calcific aortic valve disease

BMC Cardiovascular Disorders

Research

Jie Han¹  Fang wu¹  Guang-Yuan Song²  Jing Yao²  Zhi-Nan Lu²  Jia-Hong Xie²  Zhao-Lin Fu²  Jing He²  Xu-Nan Guo² 

[1] Department of Cardiac Surgery, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China;Interventional Center of Valvular Heart Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China;

关键词: Calcific Aortic Valve Disease;    Cis-regulation;    Trans-regulation;    WGCNA;    Long noncoding RNAs;    Competitive endogenous RNAs;   

DOI  :  10.1186/s12872-023-03311-x

 received in 2022-12-02, accepted in 2023-05-17,  发布年份 2023

来源: Springer

【 摘 要 】

AimTo evaluate the expression profile of long non-coding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) and explore their potential mechanism of action.MethodsThe gene expression profiles (GSE153555, GSE148219, GSE199718) were downloaded from the Gene Expression Omnibus (GEO) database and FastQC was run for quality control checks. After filtering and classifying candidate lncRNAs by differentially expressed genes (DEGs) and weighted co-expression networks (WGCNA) in GSE153555, we predicted the potential cis- or trans-regulatory target genes of differentially expressed lncRNAs (DELs) by using FEELnc and established the competitive endogenous RNA (ceRNA) network by miRanda, more over functional enrichment was analyzed using the ClusterProfiler package in R Bioconductor. The hub cis- or trans-regulatory genes were verified in GSE148219 and GSE199718 respectively.ResultsThere were 340 up-regulated lncRNAs identified in AS group compared with the control group (|log2Fold Change| ≥ 1.0 and Padj ≤ 0.05), and 460 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, twelve Long non-coding RNAs (CDKN2B-AS1, AC244453.2, APCDD1L-DT, SLC12A5-AS1, TGFB3, AC243829.4, MIR4435-2HG, FAM225A, BHLHE40-AS1, LINC01614, AL356417.2, LINC01150) were identified as the hub cis- or trans-regulatory genes in the pathogenesis of CAVD which were validated in GSE148219 and GSE19971. Additionally, we found that MIR4435-2HG was the top hub trans-acting lncRNA which also plays a crucial role by ceRNA pattern.ConclusionLncRNAs may play an important role in CAVD and may provide a new perspective on the pathogenesis, diagnosis, and treatment of this disease. Further studies are required to illuminate the underlying mechanisms and provide potential therapeutic targets.

【 授权许可】

CC BY   
© The Author(s) 2023

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