The NEAT1/miR-124-3p/CCL2 axis in chronic kidney disease progression: integrated bioinformatics analysis and experimental validation

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.
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).
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.
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.
Doctors lack good tests to track how chronic kidneydisease (CKD) gets worse over time. By studying kidney patient data, we firstfound five important substances in the body linked to CKD getting worse. One ofthese, called CCL2, had the strongest connection to the disease.
To learn how CCL2 is controlled, we studied two othermolecules that might affect it: NEAT1 (a longer molecule) and miR-124-3p (a smaller one). Our tests showed that NEAT1 “catches” miR-124-3p, stopping itfrom reducing CCL2. When we checked blood levels in 64 CKD patients, we sawthat as kidney function got worse, NEAT1 and miR-124-3p went down while CCL2went up.
These findings could lead to new blood tests tomonitor CKD and may help develop future treatments.