ABSTRACT

Cardiac remodelling is widely accepted as a common characteristic for many heart diseases, especially in heart failure (HF). Ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are associated with cardiac remodelling. Both mRNA and microRNA are potential diagnostic markers and therapeutic targets of cardiac remodelling in HF. However, the mechanisms of microRNA-mRNA joint regulation in HF are still unclear. In this study, 3 gene expression profiles from patients with and without HF were analysed to harvest shared differentially expressed genes (microRNA and mRNA) with significant major biological function. Moreover, key genes highly related to ICM and DCM-induced HF were screened out through a Weighted Genes Co-Expression Network Analysis (WGCNA). Based on microRNA-mRNA analysis, several microRNAs and target genes were identified. Combined with pathway analysis, we found that miR-542-3p and its target gene CILP were likely involved in the regulation of TGF-β signalling pathway in ICM induced HF. Collectively, the microRNA–mRNA interaction network analysis revealed that miR-542-3p-CILP as mediator of TGF-β signalling pathway might be a new mechanism to mediate ICM induced HF. This study provides certain novel targets for diagnosis and therapeutic treatment of ICM- and DCM-induced HF.

摘要

心脏重塑被广泛认为是许多心脏病的共同特征，尤其是心力衰竭 (HF)。缺血性心肌病 (ICM) 和扩张型心肌病 (DCM) 与心脏重塑有关。mRNA 和 microRNA 都是 HF 心脏重塑的潜在诊断标志物和治疗靶点。然而，HF 中 microRNA-mRNA 联合调控的机制仍不清楚。在这项研究中，分析了 HF 患者和非 HF 患者的 3 个基因表达谱，以收获具有显着主要生物学功能的共享差异表达基因（microRNA 和 mRNA）。此外，通过加权基因共表达网络分析（WGCNA）筛选出与ICM和DCM诱导的HF高度相关的关键基因。基于 microRNA-mRNA 分析，鉴定了几种 microRNA 和靶基因。结合通路分析，我们发现miR-542-3p及其靶基因CILP可能参与ICM诱导的HF中TGF-β信号通路的调控。总的来说，microRNA-mRNA相互作用网络分析表明，miR-542-3p-CILP作为TGF-β信号通路的介质可能是介导ICM诱导的HF的新机制。该研究为 ICM 和 DCM 诱导的 HF 的诊断和治疗提供了某些新的靶点。