Interventional Center of Valvular Heart Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China.
Department of Cardiac Surgery, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China.
BMC Cardiovasc Disord. 2023 Jun 27;23(1):326. doi: 10.1186/s12872-023-03311-x.
To evaluate the expression profile of long non-coding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) and explore their potential mechanism of action.
The 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.
There were 340 up-regulated lncRNAs identified in AS group compared with the control group (|logFold Change| ≥ 1.0 and P ≤ 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.
LncRNAs 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.
评估长链非编码 RNA（lncRNAs）在钙化性主动脉瓣疾病（CAVD）中的表达谱，并探讨其潜在的作用机制。
从基因表达综合数据库（GEO）下载基因表达谱（GSE153555、GSE148219、GSE199718），并使用 FastQC 进行质量控制检查。通过对 GSE153555 中差异表达基因（DEGs）和加权共表达网络（WGCNA）筛选和分类候选 lncRNAs，我们使用 FEELnc 预测差异表达 lncRNAs（DELs）的潜在顺式或反式调控靶基因，并通过 miRanda 建立竞争性内源 RNA（ceRNA）网络，进一步使用 R Bioconductor 中的 ClusterProfiler 包进行功能富集分析。分别在 GSE148219 和 GSE199718 中验证了关键的顺式或反式调控基因。
与对照组相比，AS 组有 340 个上调的 lncRNAs（|logFold Change|≥1.0，P≤0.05），460 个下调的 lncRNAs。基于靶基因预测和共表达网络构建，确定了 12 个长链非编码 RNA（CDKN2B-AS1、AC244453.2、APCDD1L-DT、SLC12A5-AS1、TGFB3、AC243829.4、MIR4435-2HG、FAM225A、BHLHE40-AS1、LINC01614、AL356417.2、LINC01150）作为 CAVD 发病机制中的关键顺式或反式调控基因，这些基因在 GSE148219 和 GSE19971 中得到了验证。此外，我们发现 MIR4435-2HG 是顶级关键反式作用 lncRNA，通过 ceRNA 模式发挥关键作用。
lncRNAs 可能在 CAVD 中发挥重要作用，并为该疾病的发病机制、诊断和治疗提供新的视角。需要进一步研究以阐明潜在的机制并提供潜在的治疗靶点。
