整合转录组分析揭示哮喘发病机制中tsRNA-mRNA调控轴的网络调控机制

Abstract

Background Asthma is a complex respiratory disorder with incompletely understood molecular mechanisms. tRNA-derived small RNAs (tsRNAs), a newly discovered class of non-coding RNAs, have been implicated in various diseases, but their role in asthma pathogenesis remains largely unexplored. Methods We performed an integrated analysis of tsRNA and mRNA profiles in bronchial epithelial cells from severe asthma patients (GSE85215, GSE85214) and healthy controls. Differentially expressed tsRNAs were identified using MINTmap and DESeq2 ( P < 0.05, |FC| > 1.5), and their target mRNAs were predicted via miRanda and TargetScan. Validation was conducted in an independent cohort (GSE201955). Functional interactions were assessed using a tsRNA–mRNA regulatory network, and key findings were experimentally confirmed in house dust mite (HDM)-stimulated BEAS-2B cells via qRT-PCR and dual-luciferase reporter assays. Results We identified 58 dysregulated tsRNAs and 961 differentially expressed mRNAs in asthma. A regulatory network revealed 343 negatively correlated tsRNA–mRNA pairs, with 36 hub mRNAs validated in GSE201955. Three candidate tsRNAs (tRF-18-SX73IE03, tRF-22-BZBZOS4Y1, tRF-22-MI7O3B1N4) showed consistent dysregulation in HDM-exposed cells. Mechanistically, tRF-21-Z4NY2V7KE directly suppressed MYBL1 expression, as confirmed by luciferase assays. Conclusions Our study provides the first comprehensive tsRNA–mRNA regulatory network in asthma, uncovering novel post-transcriptional mechanisms in bronchial epithelial cells. The identified tsRNAs and their targets may be potential biomarkers; moreover, they warrant further investigation as therapeutic targets for asthma.