Integrative bulk transcriptomic analysis and experiment validation reveals the landscape of 13 RNA modifications-associated key genes in allergic rhinitis

<title>Abstract</title> <p>Background Allergic rhinitis (AR) is strongly associated with 13 RNA modifications (RM). However, the mechanisms of action of RM on AR have not been clarified. Therefore, exploring the key genes associated with RM-related genes (RM-RGs) in AR is important. Methods The transcriptomic dataset for AR, along with 114 RM-RGs, was sourced from public databases. key genes were screened using differential expression analysis, two machine learning algorithms (Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE)), expression verification, and receiver operating characteristic (ROC) analysis. Then, gene set enrichment analysis (GSEA), immune factor analysis, molecular regulatory network construction and drug prediction, and molecular docking were performed based on key genes. Finally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) verified the expression of these key genes in clinical samples. Results CRNN, SMN1, and UPK1B were identified as key genes of AR. In the AR samples, the expression levels of CRNN, SMN1, and UPK1B were significantly reduced (p &lt; 0.05). CRNN, SMN1, and UPK1B are co-enriched in translation and RNA translation. Immune factor analysis showed that RAET1E correlated most strongly with UPK1B, with a coefficient of 0.86, p &lt; 0.001. In contrast, CRNN predicted a total of 65 TFs; SMN1 predicted a total of 53 TFs; UPK1B predicted a total of 106 TFs. A total of 146 drugs were predicted, with drugs targeting three key genes simultaneously, including Tobacco Smoke, Acetaminophen, bisphenol A, Benzo(a)pyrene, and perfluorooctanoic acid. Finally, RT-qPCR verified the expression levels of these key genes in clinical samples, consistent with bioinformatic findings. Conclusion This study identifies CRNN, SMN1, and UPK1B as highly accurate diagnostic key genes for AR. Their involvement in translation regulation and immune modulation offers a foundation for targeted therapies and precision medicine.</p>