CCR7及其相关分子可能是肺动脉高压的潜在生物标志物。
CCR7 and its related molecules may be potential biomarkers of pulmonary arterial hypertension.
作者信息
Cai Mengsi, Li Xiuchun, Dong Haoru, Wang Ying, Huang Xiaoying
机构信息
Key Laboratory of Heart and Lung, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China.
出版信息
FEBS Open Bio. 2021 Jun;11(6):1565-1578. doi: 10.1002/2211-5463.13130. Epub 2021 May 12.
Pulmonary arterial hypertension (PAH) is a chronic progressive cardiovascular disease characterized by vascular remodeling and leading to right-heart failure. The purpose of this research was to further study the pathogenesis of PAH and to detect potential prognostic signatures. Differentially expressed genes (DEGs) selected from GSE38267 were mostly enriched in inflammation-related pathways, suggesting inflammation may be involved in the occurrence and development of PAH. Through the prediction and verification of related miRNAs and long noncoding RNAs using online databases and Gene Expression Omnibus (GEO) datasets, CCR7 and its related molecules, including hsa-let-7e-5p and SNHG12, were identified as possible targets. The expression levels of CCR7, hsa-let-7e-5p and SNHG12 were then verified by quantitative RT-PCR in vivo and in vitro. Further study showed that silencing of SNHG12 decreased the expression of CCR7 under hypoxia treatment in vitro. Dual-luciferase reporter assays were used to verify the relationship between hsa-let-7e-5p and SNHG12. Collectively, our research reveals that a long noncoding RNA-miRNA-mRNA interaction network may be involved in the pathogenesis of PAH and suggests SNHG12, hsa-let-7e-5p and CCR7 as potential biomarkers for PAH.
肺动脉高压(PAH)是一种慢性进行性心血管疾病,其特征为血管重塑并导致右心衰竭。本研究的目的是进一步探究PAH的发病机制并检测潜在的预后标志物。从GSE38267中筛选出的差异表达基因(DEGs)大多富集于炎症相关通路,提示炎症可能参与PAH的发生发展。通过利用在线数据库和基因表达综合数据库(GEO)数据集对相关微小RNA(miRNAs)和长链非编码RNA进行预测及验证,CCR7及其相关分子,包括hsa-let-7e-5p和SNHG12,被确定为可能的靶点。随后通过定量逆转录聚合酶链反应(RT-PCR)在体内和体外验证了CCR7、hsa-let-7e-5p和SNHG12的表达水平。进一步研究表明,在体外缺氧处理条件下,沉默SNHG12可降低CCR7的表达。采用双荧光素酶报告基因检测法验证hsa-let-7e-5p与SNHG12之间的关系。总体而言,我们的研究揭示了一个长链非编码RNA-微小RNA-信使核糖核酸相互作用网络可能参与PAH的发病机制,并提示SNHG12、hsa-let-7e-5p和CCR7作为PAH的潜在生物标志物。
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