Identification of core noncoding RNA-associated competing endogenous RNA networks in renal fibrosis via whole-transcriptome sequencing

Objective This study aimed to investigate noncoding RNA (ncRNA) expression changes in renal fibrosis (RF) models induced by three distinct etiologies using whole-transcriptome RNA sequencing, identify overlapping differentially expressed (DE) ncRNAs, construct core competing endogenous RNA (ceRNA) n...

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Main Authors: Yizhen Chen, Meng Cheng, Rong Dai, Weili Wang, Yonghao Sang, Liuting Wei, Yilin Gao, Wei Zhang, Yiping Wang, Lei Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2522973
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Summary:Objective This study aimed to investigate noncoding RNA (ncRNA) expression changes in renal fibrosis (RF) models induced by three distinct etiologies using whole-transcriptome RNA sequencing, identify overlapping differentially expressed (DE) ncRNAs, construct core competing endogenous RNA (ceRNA) networks, and explore their role in RF.Methods Three RF rat models, 5/6 nephrectomy, adenine, and unilateral ureteral obstruction, were established. DE RNAs were identified through sequencing and validated by real-time quantitative polymerase chain reaction. ceRNA and RNA-binding protein (RBP) networks were visualized using Cytoscape. Core ceRNA axes were validated with dual-luciferase assay, RNA fluorescence in situ hybridization, western blot, immunofluorescence, and immunohistochemistry. Enrichment analysis was performed to explore potential functions.Results Sequencing analysis revealed significant dysregulation of ncRNAs in all models compared to the normal group. Intersection analysis identified 215 mRNAs, 19 lncRNAs, and 247 circRNAs as overlapping DE RNAs. lncRNA-based ceRNA networks comprising 7 lncRNAs, 8 miRNAs, and 21 mRNAs, and circRNA-based networks comprising 13 circRNAs, 29 miRNAs, and 41 mRNAs were constructed. The TCONS_00008870/circRNA_3140–miR-466b-3p–Adamts2 axis was identified as a key regulatory pathway. Enrichment analysis showed significant pathways including Rap1 signaling, extracellular matrix–receptor interaction, and PI3K-Akt signaling, with RBPs enriched in RNA binding and ferroptosis.Conclusion By integrating data from three distinct models, we identified conserved ceRNA axis—TCONS_00008870/circRNA_3140–miR-466b-3p–Adamts2—potentially modulating fibrotic progression in renal tissue.
ISSN:0886-022X
1525-6049