Sun Yifan, Xiao Zhongbo, Chen Yequn, Xu Duanmin, Chen Shuying
Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Front Cell Dev Biol. 2022 Feb 1;9:822465. doi: 10.3389/fcell.2021.822465. eCollection 2021.
We attempted to identify a regulatory competing endogenous RNA (ceRNA) network and a hub gene of Hypertrophic Cardiomyopathy (HCM). Microarray datasets of HCM tissue were obtained from NCBI Gene Expression Omnibus (GEO) database. The R package "limma" was used to identify differentially expressed genes. Online search databases were utilized to match the relation among differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs. Weighted correlation network analysis (WGCNA) was used to identify the correlations between key modules and HCM. STRING database was applied to construct PPI networks. Gene Set Enrichment Analysis (GSEA) was used to perform functional annotations and verified the hub genes. A total of 269 DE-lncRNAs, 63 DE-miRNAs and 879 DE-mRNAs were identified in myocardial tissues from microarray datasets GSE130036, GSE36946 and GSE36961, respectively. According to online databases, we found 1 upregulated miRNA hsa-miR-184 that was targeted by 2 downregulated lncRNAs (SNHG9, AC010980.2), potentially targeted 2 downregulated mRNAs (LRRC8A, SLC7A5). 3 downregulated miRNAs (hsa-miR-17-5p, hsa-miR-876-3p, hsa-miR-139-5p) that were targeted by 9 upregulated lncRNAs, potentially targeted 21 upregulated mRNAs. Black and blue modules significantly related to HCM were identified by WGCNA. Hub gene IGFBP5 regulated by hsa-miR-17-5p, AC007389.5, AC104667.1, and AC002511.2 was identified. GSEA indicated that IGFBP5 might involve in the synthesis of myosin complex, participate in kinesin binding, motor activity and function via the regulation of actin cytoskeleton. The results provide a potential molecular regulatory mechanism for the diagnosis and treatment of HCM. IGFBP5 might play an important role in the progression of HCM.
我们试图鉴定肥厚型心肌病（HCM）的一个调控性竞争性内源RNA（ceRNA）网络和一个枢纽基因。从NCBI基因表达综合数据库（GEO）获取HCM组织的微阵列数据集。使用R包“limma”鉴定差异表达基因。利用在线搜索数据库匹配差异表达的长链非编码RNA（lncRNA）、微小RNA（miRNA）和信使RNA（mRNA）之间的关系。采用加权基因共表达网络分析（WGCNA）鉴定关键模块与HCM之间的相关性。应用STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络。使用基因集富集分析（GSEA）进行功能注释并验证枢纽基因。分别在微阵列数据集GSE130036、GSE36946和GSE36961的心肌组织中鉴定出269个差异表达lncRNA、63个差异表达miRNA和879个差异表达mRNA。根据在线数据库，我们发现1个上调的miRNA hsa-miR-184被2个下调的lncRNA（SNHG9、AC010980.2）靶向，可能靶向2个下调的mRNA（LRRC8A、SLC7A5）。3个下调的miRNA（hsa-miR-17-5p、hsa-miR-876-3p、hsa-miR-139-5p）被9个上调的lncRNA靶向，可能靶向21个上调的mRNA。通过WGCNA鉴定出与HCM显著相关的黑色和蓝色模块。鉴定出受hsa-miR-17-5p、ACXX7389.5、AC104667.1和AC002511.2调控的枢纽基因胰岛素样生长因子结合蛋白5（IGFBP5）。GSEA表明，IGFBP5可能通过调节肌动蛋白细胞骨架参与肌球蛋白复合物的合成，参与驱动蛋白结合、运动活性和功能。这些结果为HCM的诊断和治疗提供了一种潜在的分子调控机制。IGFBP5可能在HCM的进展中起重要作用。
