Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Institute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Int J Mol Sci. 2022 Oct 9;23(19):11994. doi: 10.3390/ijms231911994.
Ischemic cardiomyopathy (ICM), which increases along with aging, is the leading cause of heart failure. Currently, immune response is believed to be critical in ICM whereas the roles of immune-related lncRNAs remain vague. In this study, we aimed to systematically analyze immune-related lncRNAs in the aging-related disease ICM. Here, we downloaded publicly available RNA-seq data from ischemic cardiomyopathy patients and non-failing controls (GSE116250). Weighted gene co-expression network analysis (WGCNA) was performed to identify key ICM-related modules. The immune-related lncRNAs of key modules were screened by co-expression analysis of immune-related mRNAs. Then, a competing endogenous RNA (ceRNA) network, including 5 lncRNAs and 13 mRNAs, was constructed using lncRNA-mRNA pairs which share regulatory miRNAs and have significant correlation. Among the lncRNA-mRNA pairs, one pair () was verified in another publicly available ICM dataset (GSE46224) and ischemic cell model. Further, the immune cell infiltration analysis of the GSE116250 dataset revealed that the proportions of monocytes and CD8 T cells were negatively correlated with the expression of , while plasma cells were positively correlated, indicating that may participate in the occurrence and development of ICM through immune cell infiltration. Together, our findings revealed that lncRNA-mRNA pair may be a novel biomarker and therapeutic target for ICM.
缺血性心肌病（ICM）随着年龄的增长而增加，是心力衰竭的主要原因。目前，免疫反应被认为在 ICM 中至关重要，而免疫相关长链非编码 RNA（lncRNA）的作用仍不清楚。在这项研究中，我们旨在系统分析与衰老相关疾病 ICM 相关的免疫相关 lncRNA。在这里，我们从缺血性心肌病患者和非衰竭对照（GSE116250）中下载了公开可用的 RNA-seq 数据。进行加权基因共表达网络分析（WGCNA）以识别关键的 ICM 相关模块。通过免疫相关 mRNAs 的共表达分析筛选关键模块的免疫相关 lncRNAs。然后，使用具有调控 miRNA 且具有显著相关性的 lncRNA-mRNA 对构建竞争性内源性 RNA（ceRNA）网络，包括 5 个 lncRNA 和 13 个 mRNAs。在 lncRNA-mRNA 对中，一对（）在另一个公开的 ICM 数据集（GSE46224）和缺血性细胞模型中得到了验证。此外，GSE116250 数据集的免疫细胞浸润分析表明，单核细胞和 CD8 T 细胞的比例与 的表达呈负相关，而浆细胞呈正相关，表明 可能通过免疫细胞浸润参与 ICM 的发生和发展。总之，我们的研究结果表明，lncRNA-mRNA 对 可能是 ICM 的一种新的生物标志物和治疗靶点。
