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The NEAT1/miR-124-3p/CCL2 axis in chronic kidney disease progression: integrated bioinformatics analysis and
Guanting Chen1,2, Linqi Zhang1,2, Yaoxian Wang2
1Department of Nephrology, First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, China.
Background:
Chronickidney disease (CKD) is a major global health burden lacking effectivetherapies. Renal interstitial fibrosis (RIF) is a key pathological driver ofCKD progression. This study aimed to identify novel diagnostic biomarkers and therapeutictargets.
Research Design And Methods:
Weanalyzed the GEO dataset GSE137570 to identify differentially expressed genes(DEGs). Protein-protein interaction (PPI) networks were constructed to screen HubGenes. A competing endogenous RNA (ceRNA) network was predicted. Validationincluded single-cell sequencing, in vitro epithelial-mesenchymal transition(EMT) models using Transforming growth factor-β 1 (TGF-β1)-treated TCMK1 cells,clinical samples (64 CKD patients, 20 healthy controls), and dual-luciferasereporter assays (DLRA).
Results:
FiveHub Genes (EGF, VCAN, CXCL1, MMP7, CCL2) were identified, with CCL2 being themost central. Enrichment analyses linked them to immune/inflammatory responses.DLRA confirmed specific targeting between miR-124-3p and both NEAT1 and CCL2,supporting the NEAT1/miR-124-3p/CCL2 axis. Clinically, serum CCL2 increasedwhile miR-124-3p and NEAT1 decreased with CKD progression; all three showedgood diagnostic accuracy for staging.
Conclusions:
EGF,VCAN, CXCL1, MMP7, and particularly CCL2 are potential CKDbiomarkers/therapeutic targets. The NEAT1/miR-124-3p/CCL2 axis is a keyregulatory pathway in CKD. Key limitations include the moderate sample sizes inbioinformatics and clinical cohorts.
Insights
Researchers identified key genes, including CCL2, as potential biomarkers and therapeutic targets for chronic kidney disease (CKD). A regulatory axis involving NEAT1, miR-124-3p, and CCL2 was found to be crucial in CKD progression.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics
Background:
- Chronic kidney disease (CKD) represents a significant global health challenge with limited effective treatments.
- Renal interstitial fibrosis (RIF) is a primary driver of CKD progression.
- The study sought to discover novel diagnostic biomarkers and therapeutic targets for CKD.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) and key regulatory pathways in CKD.
- To validate potential biomarkers and therapeutic targets using various experimental models and clinical samples.
- To elucidate the role of the NEAT1/miR-124-3p/CCL2 axis in CKD pathogenesis.
Main Methods:
- Analysis of the GEO dataset GSE137570 to identify DEGs.
- Construction of protein-protein interaction (PPI) networks to screen Hub Genes.
- Prediction of a competing endogenous RNA (ceRNA) network and validation through single-cell sequencing, in vitro EMT models, clinical samples, and dual-luciferase reporter assays (DLRA).
Main Results:
- Five Hub Genes (EGF, VCAN, CXCL1, MMP7, CCL2) were identified, with CCL2 being the most central.
- Enrichment analyses indicated a link between these genes and immune/inflammatory responses.
- The NEAT1/miR-124-3p/CCL2 axis was confirmed, with serum CCL2 increasing and miR-124-3p and NEAT1 decreasing with CKD progression; these factors demonstrated diagnostic accuracy for staging.
Conclusions:
- CCL2, alongside EGF, VCAN, CXCL1, and MMP7, shows promise as a CKD biomarker and therapeutic target.
- The NEAT1/miR-124-3p/CCL2 axis is a critical regulatory pathway implicated in CKD.
- Moderate sample sizes in bioinformatics and clinical cohorts represent key limitations for future research.
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