Diagnostic model construction of mitochondrial-mitophagy related genes and their regulatory network and potential drug discovery in childhood allergic asthma

Childhood allergic asthma (CAA) is a chronic airway inflammatory disorder driven by allergens, and its underlying molecular mechanisms as well as precise diagnostic and therapeutic strategies remain to be further elucidated. Based on public transcriptome datasets, this study integrated weighted gene co-expression network analysis (WGCNA) with multiple machine learning algorithms to systematically identify 15 signature genes with diagnostic potential from a panel of mitochondrial-mitophagy-related genes (MMRGs), and further established a well-performing diagnostic model for CAA. Immune infiltration analyses demonstrated that the abundances of several immune cell subsets, including resting mast cells and naive B cells, were aberrantly altered in CAA patients, and the expression levels of the signature genes were significantly correlated with multiple immune cell populations, implying their potential involvement in the regulation of the immune microenvironment. The subsequently constructed ceRNA regulatory network uncovered the sophisticated post-transcriptional regulatory mechanisms of these signature genes, whereas drug-gene interaction analysis predicted numerous potential targeted agents, among which BCL2-related compounds were the most abundant. In vitro experiments revealed that in IL-13-stimulated airway epithelial cell models, MRPL43 expression was upregulated while BCL2 expression was downregulated; moreover, knockdown of MRPL43 markedly restored cell viability and suppressed the secretion of pro-inflammatory cytokines. Collectively, this study systematically delineated the crucial roles of MMRGs in CAA covering the identification of molecular biomarkers, dissection of immunological mechanisms, and exploration of potential therapeutic targets, thereby providing novel theoretical insights and research directions for the early diagnosis and individualized treatment of this disease.