Circ_0001185 as a novel therapeutic target for lupus nephritis according to ceRNA network comprehensive analysis

This study aimed to investigate the regulatory role of circular RNAs (circRNAs) in lupus nephritis (LN) and to explore their potential mechanisms.

Renal tissue circRNA, miRNA, and mRNA expression profiles were obtained from GEO datasets. Differentially expressed RNAs were analyzed using R software to construct a circRNA-miRNA-mRNA network. Functional enrichment analysis was performed. Correlations between key gene expression and clinical features were analyzed using the Nephroseq V5 database and validated by immunohistochemistry in an independent LN cohort. CIBERSORT was used to explore immune cell infiltration and analyze the correlations between key genes and immune cell types.

Based on the predicted correlations among differentially expressed circRNAs, miRNAs, and mRNAs, a ceRNA network was constructed. Among the six circRNAs with multiple miRNA binding sites, circ_0001185, which is derived from the IFNGR2 gene, was predicted to act as a sponge for miR-30b-5p. In the network, miR-30b-5p, miR-33a-3p, and miR-103a-2-5p exhibited the highest node degrees. And NFAT5 was identified as a common downstream target of both miR-30b-5p and miR-103a-2-5p. Analysis of the Nephroseq V5 dataset revealed that elevated expression of IFNGR2 and NFAT5 in renal tissue was negatively correlated with eGFR. Immunohistochemistry showed increased NFAT5 expression in renal tissues of LN patients, particularly in proliferative LN, and which was positively correlation with neutrophil infiltration. Furthermore, activated dendritic cells and naive CD4 + T cells showed a positive correlation in CIBERSORT analysis.

This study constructed a circRNA-miRNA-mRNA ceRNA network and identified a potential circ_0001185/miR-30b-5p/NFAT5 regulatory axis in LN. Bioinformatic analysis suggested that circ_0001185 may have peptide-coding potential, a preliminary observation that warrants further exploration. Together, these findings identify circ_0001185 as a candidate for future functional studies to evaluate its therapeutic potential. Key Points • This study identifies a potential circ_0001185/miR-30b-5p/NFAT5 regulatory axis in LN, which may be associated with Th17 cell differentiation. IFNGR2 and NFAT5 are associated with eGFR, and bioinformatic analysis raises the possibility that circ_0001185 may have peptide-coding potential, suggesting it warrants further exploration as a candidate for therapeutic investigation.