Weighted miRNA co-expression network reveals potential roles of apoptosis related pathways and crucial genes in thoracic aortic aneurysm

Siliang Chen; Lei Ji; Mengyin Chen; Dan Yang; Jiawei Zhou; Yuehong Zheng

doi:10.21037/jtd-20-3601

Weighted miRNA co-expression network reveals potential roles of apoptosis related pathways and crucial genes in thoracic aortic aneurysm

J Thorac Dis. 2021 May;13(5):2776-2789. doi: 10.21037/jtd-20-3601.

Authors

Siliang Chen¹, Lei Ji¹, Mengyin Chen¹, Dan Yang², Jiawei Zhou¹, Yuehong Zheng¹

Affiliations

¹ Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Computational Biology and Bioinformatics, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background: Thoracic 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.

Methods: Differentially 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.

Results: The 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.

Conclusions: We 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.

Keywords: Thoracic aortic aneurysm (TAA); apoptosis; miRNA; weighted correlation network analysis (WGCNA).