Research Paper Volume 14, Issue 9 pp 4085—4106
A novel lncRNA-miRNA-mRNA triple network identifies lncRNA XIST as a biomarker for acute myocardial infarction
- 1 Cardiology Department, Hunan Provincial People's Hospital, Furong District, Changsha 410000, Hunan, China
- 2 Clinical Research Center for Heart Failure in Hunan Province, Furong District, Changsha 410000, Hunan, China
- 3 Institute of Cardiovascular Epidemiology, Hunan Provincial People's Hospital, Furong District, Changsha 410000, Hunan, China
- 4 Department of Cardiology, The Central Hospital of ShaoYang, Daxiang District, Shaoyang 422000, Hunan, China
Received: February 22, 2022 Accepted: April 16, 2022 Published: May 10, 2022
https://doi.org/10.18632/aging.204075How to Cite
Copyright: © 2022 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Despite the well-established role of long non-coding RNAs (lncRNAs) across various biological processes, their mechanisms in acute myocardial infarction (AMI) are not fully elucidated. The GSE34198 dataset from the Gene Expression Omnibus (GEO) database, which comprised 49 specimens from individuals with AMI and 47 specimens from controls, was extracted and analysed using the weighted gene co-expression network analysis (WGCNA) package. Twenty-seven key genes were identified through a combination of the degree and gene significance (GS) values, and the CDC42 (degree = 64), JAK2 (degree = 41), and CHUK (degree = 30) genes were identified as having the top three-degree values among the 27 genes. Potential interactions between lncRNA, miRNAs and mRNAs were predicted using the starBase V3.0 database, and a lncRNA-miRNA-mRNA triple network containing the lncRNA XIST, twenty-one miRNAs and three hub genes (CDC42, JAK2 and CHUK) was identified. RT–qPCR validation showed that the expression of the JAK2 and CDC42 genes and the lncRNA XIST was noticeably increased in samples from patients with AMI compared to normal samples. Pearson’s correlation analysis also proved that JAK2 and CDC42 expression levels correlated positively with lncRNA XIST expression levels. The area under ROC curve (AUC) of lncRNA XIST was 0.886, and the diagnostic efficacy of the lncRNA XIST was significantly better than that of JAK2 and CDC42. The results suggested that the lncRNA XIST appears to be a risk factor for AMI likely through its ability to regulate JAK2 and CDC42 gene expressions, and it is expected to be a novel and reliable biomarker for the diagnosis of AMI.
Abbreviations
WGCNA: weighted gene co-expression network analysis; XIST: X inactive specific transcript; CAD: coronary artery disease; GS: gene significance; AMI: acute myocardial infarction; DAVID: Database for Annotation, Visualization and Integrated Discovery; T2DM: Type 2 diabetes mellitus; GO: Gene Ontology; HDL-C: High-density lipoprotein cholesterol; IS: Ischemic stroke; KEGG: Kyoto Encyclopedia of Genes and genomes; LDL-C: Low-density lipoprotein cholesterol; MCODE: Molecular Complex Detection; Apo: Apolipoprotein; PPI: Protein-protein interaction; GEO: Gene Expression Omnibus; BMI: Body mass index; TG: Triglyceride; RT-qPCR: Quantitative real time polymerase chain reaction; TC: Total cholesterol; PCI: percutaneous coronary intervention; ncRNAs: non-coding RNAs; lncRNAs: long ncRNAs; lincRNAs: long intergenic ncRNAs; WISPER: wisp2 super enhancer related RNA; TOM: topological overlap matrix; Mes: module eigengenes; MM: module membership; STRING: Search Tool for the Retrieval of Interacting Genes; CK-MB: creatine kinase-MB; cTns: cardiac troponins; CVD: cardiovascular diseases; MM: module membership; OSMR-β: oncostatin M receptor β; FNDC5: Fibronectin type III domain containing 5; TLR2: toll-like receptor 2.