Integrated ceRNA Network Analysis Reveals Molecular Pathogenesis of Arteriovenous Fistula Dysfunction

Ming Zhao¹Shuiling Chen²Wanjun Li¹Rui Nian¹Wei Chen^1*Hongzhao Lu^2*

• ¹3201 Hospital, Hanzhong, China
• ²Shaanxi University of Technology, Hanzhong, China

Abstract Background: Vascular access fistula (AVF) stenosis is a common complication in hemodialysis patients, leading to access failure. This study aimed to explore the molecular mechanisms involved in AVF stenosis, focusing on the circRNA-miRNA-mRNA regulatory network. Methods: This study was performed on paired samples (12 pre-access veins and 12 stenotic AVFs) obtained from 12 patients. RNA sequencing was conducted to analyze gene expression profiles, followed by bioinformatic analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to uncover potential regulatory networks involved in processes such as the inflammatory response. Results:Differentially expressed circRNAs, miRNAs, and mRNAs were identified, with several genes significantly enriched in pathways related to inflammation and vascular remodeling. The identified regulatory network highlights miR-382-5p, miR-146b-3p, CREB3L1, and RXFP1 as potential key mediators of vascular smooth muscle cell (VSMC) proliferation, extracellular matrix deposition, and inflammatory responses during vascular remodeling.Potential interactions between circRNAs, miRNAs, and mRNAs were predicted, suggesting a complex regulatory network involved in AVF stenosis.Predicted interactions among circRNAs, miRNAs, and mRNAs suggest the presence of a complex ceRNA network contributing to AVF stenosis. Protein – protein interaction (PPI) analysis further identified COL1A1, COL3A1, MMP9, and IL-1 β as central regulators of ECM remodeling and inflammation. Notably, circCAMK2G and circUNC13C emerged as major ceRNA hubs associated with calcium signaling and endothelial dysfunction via miR-665 and miR-301a-5p, respectively. Conclusions: our study reveals a complex circRNA-miRNA-mRNA regulatory network in AVF stenosis. These findings suggest its potential role in the pathophysiology of stenosis, including neointimal hyperplasia (a process often characterized by VSMC proliferation), and provide candidate targets for future in-depth functional mechanistic studies.However, as these findings are 2 computationally derived, they should be regarded as preliminary and require experimental validation. Future studies with larger sample sizes and appropriate functional models are needed to confirm and expand upon these findings.