Research Paper Volume 15, Issue 21 pp 12155—12170

Identification of circRNA-miRNA-mRNA network as biomarkers for interstitial cystitis/bladder pain syndrome

Shi-Qin Yang1, *, , Liao Peng1, *, , Le-De Lin1, , Yuan-Zhuo Chen1, , Meng-Zhu Liu1, , Chi Zhang1, , Jia-Wei Chen1, , De-Yi Luo1, ,

  • 1 Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
* Equal contribution

Received: August 7, 2023       Accepted: October 8, 2023       Published: November 2, 2023
How to Cite

Copyright: © 2023 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Interstitial cystitis/bladder pain syndrome (IC/BPS) is a long-lasting and incapacitating disease, and the exact factors that affect its onset and advancement are still uncertain. Thus, the main aim was to explore new biomarkers and possible therapeutic targets for IC/BPS. Next-generation high-throughput sequencing experiments were performed on bladder tissues. Based on the interactions between circRNA and miRNA, as well as miRNA and mRNA, candidates were selected to build a network of circRNA-miRNA-mRNA. The STRING database and Cytoscape software were utilized to build a protein-protein interaction (PPI) network to pinpoint the hub genes associated with IC/BPS. The expression levels of circRNA and miRNA in the network were confirmed through quantitative polymerase chain reaction. Western blot was applied to confirm the stability of the lipopolysaccharide-induced IC/BPS model, and the effect of overexpression of circ.5863 by lentivirus on inflammation. Ten circRNA-miRNA interactions involving three circRNAs and six miRNAs were identified, and IFIT3 and RSAD2 were identified as hub genes in the resulting PPI network with 19 nodes. Circ.5863 showed a statistically significant decrease in the constructed model, which is consistent with the sequencing results, and overexpression via lentiviral transfection of circ.5863 was found to alleviate inflammation damage. In this study, a circRNA-miRNA-mRNA network was successfully constructed, and IFIT3 and RSAD2 were identified as hub genes. Our findings suggest that circ.5863 can mitigate inflammation damage in IC/BPS. The identified marker genes may serve as valuable targets for future research aimed at developing diagnostic tools and more effective therapies for IC/BPS.


IC/BPS: Interstitial cystitis/bladder pain syndrome; PPI: protein-protein interaction; circRNA: Circular RNA; EMT: epithelial-mesenchymal transition; DEcircRNAs: CircRNAs exhibiting differential expression; DEmiRNAs: miRNAs exhibiting differential expression; DEmRNAs: mRNAs exhibiting differential expression; FPKM: Fragments Per Kilobase of exon model per Million mapped; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; DAVID: Database for Annotation, Visualization, and Integration Discovery; HUCs: human urothelial cells; LPS: Lipopolysaccharide; qPCR: quantitative polymerase chain reaction; PSUI: pure stress urinary incontinence.