Wu Qiuhong, Liu Yang, Xie Yan, Wei Shixiong, Liu Yi
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China.
Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2021 Jun 17;9:622021. doi: 10.3389/fcell.2021.622021. eCollection 2021.
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is one of the most severe complications of systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. However, the precise pathogenesis of pulmonary fibrosis in SSc-ILD remains unknown. This study aimed to evaluate the competing endogenous RNA (ceRNA) regulatory network and immune cell infiltration patterns in SSc-ILD.
One microRNA (miRNA) and three messenger RNA (mRNA) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed miRNAs (DEmiRs) and mRNAs (DEMs) between SSc-ILD patients and normal controls were identified, respectively, followed by the prediction of the target genes and target lncRNAs of DEmiRs. The overlapping genes between DEmiRs target genes and DEMs were identified as core mRNAs to construct the ceRNA network. In addition, the "Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)" algorithm was used to analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients and controls, and differentially expressed immune cells were recognized. The correlation between immune cells and core mRNAs was evaluated by Pearson correlation analysis.
Totally, 42 SSc-ILD lung tissues and 18 normal lung tissues were included in this study. We identified 35 DEmiRs and 142 DEMs and predicted 1,265 target genes of DEmiRs. Then, 9 core mRNAs related to SSc-ILD were recognized, which were the overlapping genes between DEmiRs target genes and DEMs. Meanwhile, 9 DEmiRs related to core mRNAs were identified reversely, and their target lncRNAs were predicted. In total, 9 DEmiRs, 9 core mRNAs, and 51 predicted lncRNAs were integrated to construct the ceRNA regulatory network of SSc-ILD. In addition, 9 types of immune cells were differentially expressed in lung tissues between SSc-ILD patients and controls. Some core mRNAs, such as , , and , were positively or negatively correlated with the number of infiltrating immune cells.
This is the first comprehensive study to construct the potential ceRNA regulatory network and analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients, which improves our understanding of the pathogenesis of SSc-ILD.
系统性硬化症相关间质性肺疾病（SSc-ILD）是系统性硬化症（SSc）最严重的并发症之一，也是SSc相关死亡的主要原因。然而，SSc-ILD中肺纤维化的确切发病机制仍不清楚。本研究旨在评估SSc-ILD中的竞争性内源性RNA（ceRNA）调控网络和免疫细胞浸润模式。
从基因表达综合数据库（GEO）获得一个微小RNA（miRNA）和三个信使RNA（mRNA）微阵列数据集。然后，分别鉴定SSc-ILD患者和正常对照之间差异表达的miRNA（DEmiRs）和mRNA（DEMs），接着预测DEmiRs的靶基因和靶长链非编码RNA（lncRNAs）。将DEmiRs靶基因与DEMs之间的重叠基因鉴定为核心mRNA以构建ceRNA网络。此外，使用“通过估计已知RNA转录本的相对子集进行细胞类型鉴定（CIBERSORT）”算法分析SSc-ILD患者和对照肺组织中浸润免疫细胞的组成，并识别差异表达的免疫细胞。通过Pearson相关分析评估免疫细胞与核心mRNA之间的相关性。
本研究共纳入42例SSc-ILD肺组织和18例正常肺组织。我们鉴定出35个DEmiRs和142个DEMs，并预测了1265个DEmiRs的靶基因。然后，识别出9个与SSc-ILD相关的核心mRNA，它们是DEmiRs靶基因与DEMs之间的重叠基因。同时，反向鉴定出9个与核心mRNA相关的DEmiRs，并预测了它们的靶lncRNAs。总共整合了9个DEmiRs、9个核心mRNA和51个预测的lncRNAs，构建了SSc-ILD的ceRNA调控网络。此外，SSc-ILD患者和对照的肺组织中有9种免疫细胞差异表达。一些核心mRNA，如 、 和 ，与浸润免疫细胞的数量呈正相关或负相关。
这是第一项构建潜在ceRNA调控网络并分析SSc-ILD患者肺组织中浸润免疫细胞组成的综合性研究，提高了我们对SSc-ILD发病机制的理解。
