Integrative analysis of key microRNA-mRNA complexes and pathways in aortic aneurysm

Yufei Fu; Yingying Mao; Ruoshi Chen; Anfeng Yu; Yifei Yin; Xi Wang; Liang Ma; Xin Chen

doi:10.21037/atm-22-514

Integrative analysis of key microRNA-mRNA complexes and pathways in aortic aneurysm

Ann Transl Med. 2022 Mar;10(6):358. doi: 10.21037/atm-22-514.

Authors

Yufei Fu¹, Yingying Mao², Ruoshi Chen³, Anfeng Yu³, Yifei Yin¹, Xi Wang¹, Liang Ma³, Xin Chen³

Affiliations

¹ Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, China.
² Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University, Hangzhou, China.
³ Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhejiang University, Medical School of Zhejiang University, Hangzhou, China.

Abstract

Background: This study investigated the therapeutic targets of aortic aneurysm (AA) and provided insights into the pathogenesis and molecular mechanisms of AA.

Methods: The messenger RNA (mRNA) datasets, GSE9106 (blood samples) and GSE7084 (tissue samples), and the microRNA (miRNA) datasets, GSE92427 (blood samples) and GSE110527 (tissue samples), were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were analyzed by limma. Based on the co-DEGs and co-DE-miRNAs between the AA blood and tissue datasets, the miRNA-mRNA regulatory pairs were predicted. Functional enrichment analyses and gene set enrichment analysis (GSEA) were performed and the protein-protein interaction (PPI) network was generated to further analyze the related genes and their functions. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and tyramide signal amplification (TSA)-in situ hybridization (ISH) assays were performed to detect the expression of co-DE-miRNAs in AA clinical tissue samples and normal aorta samples.

Results: There were 19 upregulated and 5 downregulated co-differential mRNAs. MiR-4306 was the upregulated co-differential miRNA, and miR-3198 was the downregulated co-differential miRNA by blood-tissue co-analysis. Based on the co-DEGs and co-DE-miRNAs, 4 miRNA-mRNA regulatory pairs were predicted. PPI networks were constructed of co-DEGs with 6 relationship pairs. RT-qPCR and TSA-ISH assays showed the upregulation of miR-4306 and the downregulation of miR-3198 in AA tissue samples.

Conclusions: This study provided evidence regarding the differential regulatory miRNA-mRNA networks in AA blood and tissue samples and identified key genes and signaling pathways related to AA, which provided insights into potential targets and mechanisms of AA pathogenesis and progression.

Keywords: Aortic aneurysm (AA); gene set enrichment analysis (GSEA); integrated analysis; microRNA-messenger RNA complex (miRNA-mRNA complex); tyramide signal amplification-in situ hybridization assay (TSA-ISH assay).