Hypoxia-immune ceRNA network identifies novel diagnostic biomarkers and therapeutic targets in pulpitis

Pulpitis is a common inflammatory condition of dental pulp tissue, but the underlying molecular mechanisms remain poorly understood. This study applied a novel hypoxia-immune integrated competing endogenous RNA (ceRNA) network approach to identify key regulatory mechanisms in pulpitis pathogenesis. RNA sequencing was performed on pulp tissues from 6 pulpitis patients and 6 healthy controls using the BGISEQ platform. Differential expression analysis identified dysregulated mRNAs, miRNAs, and lncRNAs. Hypoxia- and immune-related genes were obtained from pre-defined gene sets in the MSigDB, ImmPort, and InnateDB databases. A ceRNA network was constructed using TargetScan, miRcode, and miRDB databases, followed by identification of key regulatory axes through correlation analysis. Immune infiltration and drug target prediction analyses were performed. External validation was conducted using the GSE77459 dataset. We identified 3347 differentially expressed mRNAs, 155 miRNAs, and 2286 lncRNAs. Among these, 557 mRNAs were related to hypoxia-immune pathways. Two key regulatory axes were identified: BCYRN1-hsa-miR-25-5p-EDIL3 and BCYRN1/PCA3-hsa-miR-425-5p-MAP2K6. The regulatory factors showed significant correlations with immune checkpoints and NK cell infiltration, with hsa-miR-425-5p exhibiting positive correlations with immune checkpoints but negative correlation with NK cell infiltration, while BCYRN1 and MAP2K6 showed opposite patterns. MAP2K6 was predicted as a target for Fostamatinib. External validation confirmed the differential expression patterns, with both MAP2K6 and EDIL3 achieving perfect diagnostic performance (AUC = 1.00). This study reveals novel ceRNA regulatory mechanisms in pulpitis and identifies potential biomarkers and therapeutic targets, providing new insights into pulpitis pathogenesis and clinical management strategies.