Dataset Information

Identifying miRNA Modules and Related Pathways of Chronic Obstructive Pulmonary Disease Associated Emphysema by Weighted Gene Co-Expression Network Analysis

ABSTRACT:

Background

Chronic obstructive pulmonary disease (COPD) is a heterogeneous chronic inflammatory disease characterized by progressive airflow limitation that causes high morbidity and mortality. MicroRNA, a short-chain noncoding RNA, regulates gene expression at the transcriptional level. microRNA modules with a role in the pathogenesis of COPD may serve as COPD biomarkers.

Methods

We downloaded the GSE33336 microarray data set from the Gene Expression Omnibus (GEO) database, the data are derived from 29 lung samples of patients with emphysema undergoing curative resection for lung cancer. We used weighted gene co-expression network analysis (WGCNA) to construct co-expression modules and detect trait-related microRNA modules. We used the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to predict the biological function of the interest modules, and we screened out candidate hub microRNAs based on their module membership (MM) value and top proteins on the results of the protein–protein interaction (PPI) network.

Results

Three microRNA modules (royal blue, light yellow and grey60) were highly associated with COPD. Axon guidance, proteoglycans in cancer and mitogen-activated protein kinases (MAPK) signaling pathway were common pathways in these three modules. Keratin18 (KRT18) was the top protein in our study. miR-452, miR-149, miR-133a, miR-181a and miR-421 in hub microRNAs may play a role in COPD.

Conclusion

These findings provide evidence for the role of miRNAs in COPD and identify biomarker candidates.

SUBMITTER: An J

PROVIDER: S-EPMC8605490 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background MicroRNAs (miRNAs) have been confirmed to be inextricably linked to the emergence of human complex diseases. The identification of the disease-related miRNAs has gradually become a routine way to unveil the genetic mechanisms of examined disorders. Methods In this study, a method BLNIMDA based on a weighted bi-level network was proposed for predicting hidden associations between miRNAs and diseases. For this purpose, the known associations between miRNAs and diseases as well as integrated similarities between miRNAs and diseases are mapped into a bi-level network. Based on the developed bi-level network, the miRNA-disease associations (MDAs) are defined as strong associations, potential associations and no associations. Then, each miRNA-disease pair (MDP) is assigned two information properties according to the bidirectional information distribution strategy, i.e., associations of miRNA towards disease and vice-versa. Finally, two affinity weights for each MDP obtained from the information properties and the association type are then averaged as the final association score of the MDP. Highlights of the BLNIMDA lie in the definition of MDA types, and the introduction of affinity weights evaluation from the bidirectional information distribution strategy and defined association types, which ensure the comprehensiveness and accuracy of the final prediction score of MDAs. Results Five-fold cross-validation and leave-one-out cross-validation are used to evaluate the performance of the BLNIMDA. The results of the Area Under Curve show that the BLNIMDA has many advantages over the other seven selected computational methods. Furthermore, the case studies based on four common diseases and miRNAs prove that the BLNIMDA has good predictive performance. Conclusions Therefore, the BLNIMDA is an effective method for predicting hidden MDAs. Supplementary Information The online version contains supplementary material available at 10.1186/s12864-022-08908-8.

Project description:Background Asthma is a chronic lung disease characterized by reversible inflammation of the airways. The imbalance of Th1/Th2 cells plays a significant role in the mechanisms of asthma. The aim of this study was to identify asthma-related key genes and functionally enriched pathways in a Th2-high group by using weighted gene coexpression network analysis (WGCNA). Methods The gene expression profiles of GSE4302, which included 42 asthma patients and 28 controls, were selected from the Gene Expression Omnibus (GEO). A gene network was constructed, and genes were classified into different modules using WGCNA. Gene ontology (GO) was performed to further explore the potential function of the genes in the most related module. In addition, the expression profile and diagnostic capacity (ROC curve) of hub genes of interest were verified by dataset GSE67472. Results In dataset GSE4302, subjects with asthma were divided into Th2-high and Th2-low groups according to the expression of the SERPINB2, POSTN and CLCA1 genes. A weighted gene coexpression network was constructed, and genes were classified into 7 modules. Among them, the red module was most closely associated with Th2-high asthma, which contained 60 genes. These genes were significantly enriched in different biological processes and molecular functions. A total of 8 hub genes (TPSB2, CPA3, ITLN1, CST1, SERPINB10, CEACAM5, CHD26 and P2RY14) were identified, and the expression levels of these genes (except TPSB2) were confirmed in dataset GSE67472. ROC curve analysis validated that the expression of these 8 genes exhibited excellent diagnostic efficiency for Th2-high asthma and Th2-low asthma. Conclusions The study provides a novel perspective on Th2-high asthma by WGCNA, and the hub genes and potential pathways involved may be beneficial for the diagnosis and management of Th2-high asthma. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-022-01241-9.

Project description:BackgroundThoracic aortic aneurysm (TAA) is a potentially life-threatening disease for which few medical therapies are available. Thus, it is critically important to investigate the underlying molecular mechanisms of TAA, and identify potential targets for TAA treatment.MethodsDifferentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were screened, and a weighted correlation network analysis (WGCNA) was employed to construct a weighted miRNA co-expression network using GSE110527. The DEMs were then mapped into the whole co-expression network of all samples, and a DEM coexpression network was created. Molecular Complex Detection (MCODE) was used to identify crucial miRNAs. Target genes were predicted using the miRTarbase database, and further screened by identifying genes that overlapped with the DEGs of GSE26155. The screened target genes were validated using GSE9106, and the successfully validated genes were considered as crucial genes. Finally, a miRNA risk score for diagnosing TAA was calculated by undertaking a least absolute shrinkage and selection operator (LASSO) regression.ResultsThe tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) signaling pathway was found in DEM functional enrichment. Crucial miRNAs were identified and target genes were predicted and associated with the regulation of the TRAIL signaling pathway. Next, 113 important target genes were identified as overlapping with the DEGs of GSE26155. These genes were further validated, and 5 successfully validated genes were considered as crucial genes. Finally, the miRNA risk score calculated by the LASSO regression was shown to have potential diagnostic value.ConclusionsWe performed a WGCNA analysis to construct a weighted miRNA co-expression network, predicted target genes of crucial miRNAs, identified crucial genes, and finally calculated a miRNA risk score. The results showed that pathways and genes associated with apoptosis appear to play an important role in TAA pathogenesis, and that medications targeting apoptosis might slow TAA progression. Future in vitro and in vivo experimental studies need to be undertaken to further validate our findings and investigate the mechanistic details of these crucial miRNAs and crucial genes.