Zhang Yuan, Zhao Jiuxiao, Jin Qiao, Zhuang Lenan
Institute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China.
Int J Mol Sci. 2024 Feb 29;25(5):2816. doi: 10.3390/ijms25052816.
Hypertrophic cardiomyopathy (HCM) is a disease in which the myocardium of the heart becomes asymmetrically thickened, malformed, disordered, and loses its normal structure and function. Recent studies have demonstrated the significant involvement of inflammatory responses in HCM. However, the precise role of immune-related long non-coding RNAs (lncRNAs) in the pathogenesis of HCM remains unclear. In this study, we performed a comprehensive analysis of immune-related lncRNAs in HCM. First, transcriptomic RNA-Seq data from both HCM patients and healthy individuals (GSE180313) were reanalyzed thoroughly. Key HCM-related modules were identified using weighted gene co-expression network analysis (WGCNA). A screening for immune-related lncRNAs was conducted within the key modules using immune-related mRNA co-expression analysis. Based on lncRNA-mRNA pairs that exhibit shared regulatory microRNAs (miRNAs), we constructed a competing endogenous RNA (ceRNA) network, comprising 9 lncRNAs and 17 mRNAs that were significantly correlated. Among the 26 lncRNA-mRNA pairs, only the pair was verified by another HCM dataset (GSE130036) and the isoprenaline (ISO)-induced HCM cell model. Furthermore, knockdown of increased the regulatory miRNAs and decreased the mRNA expression of correspondingly in AC16 cells. Additionally, the analysis of immune cell infiltration indicated that the - pair was potentially involved in the infiltration of naïve CD4 T cells and CD8 T cells. Together, our findings indicate that the decreased expression of the lncRNA-mRNA pair - was significantly correlated with the pathogenesis of the disease and may be involved in the immune cell infiltration in the mechanism of HCM.
肥厚型心肌病（HCM）是一种心肌出现不对称增厚、畸形、紊乱并丧失其正常结构和功能的疾病。最近的研究表明炎症反应在HCM中起重要作用。然而，免疫相关长链非编码RNA（lncRNA）在HCM发病机制中的确切作用仍不清楚。在本研究中，我们对HCM中免疫相关lncRNA进行了全面分析。首先，对来自HCM患者和健康个体的转录组RNA测序数据（GSE180313）进行了深入重新分析。使用加权基因共表达网络分析（WGCNA）确定了与HCM相关的关键模块。在关键模块内使用免疫相关mRNA共表达分析对免疫相关lncRNA进行筛选。基于表现出共享调控微小RNA（miRNA）的lncRNA-mRNA对，我们构建了一个竞争性内源性RNA（ceRNA）网络，该网络由9个lncRNA和17个显著相关的mRNA组成。在这26个lncRNA-mRNA对中，只有该对通过另一个HCM数据集（GSE130036）和异丙肾上腺素（ISO）诱导的HCM细胞模型得到验证。此外，在AC16细胞中敲低该lncRNA增加了调控miRNA并相应降低了该mRNA的表达。另外，免疫细胞浸润分析表明该lncRNA-mRNA对可能参与了初始CD4 T细胞和CD8 T细胞的浸润。总之，我们的研究结果表明lncRNA-mRNA对的表达降低与疾病发病机制显著相关，并且可能在HCM机制中的免疫细胞浸润中起作用。
