MicroRNA sequencing analysis in pediatric patients with influenza-associated acute necrotizing encephalopathy: Potential biomarkers for early diagnosis and therapy

Acute necrotizing encephalopathy (ANE) secondary to influenza infection is characterized by fulminant neurological deterioration and a high mortality rate. The underlying mechanisms remain unclear, and specific treatments are currently lacking. Therefore, understanding the pathogenesis and identifying diagnostic and therapeutic targets for influenza-induced ANE are crucial. Peripheral blood samples were collected from two groups: influenza-infected patients without ANE (mild) and influenza infection with ANE patients (severe). Differentially expressed genes (DEG) were identified through microRNA sequencing analysis, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression levels of the four specific miRNAs were validated using qRT-PCR. In the severe group, 24 genes were up-regulated, and 67 genes were down-regulated compared to the mild group. The expression levels of hsa-miR-1290, hsa-miR-4657, has-miR-1231, and hsa-miR-342-3p were validated by qRT-PCR, and the levels of has-miR-4657 and hsamiR- 342-3p showed significant differences between severe and mild groups. GO analysis demonstrated that the DEGs were predominantly involved in the positive regulation of cellular processes, intracellular anatomical structure, and protein binding. KEGG pathway analysis revealed that DEGs were mainly enriched in calcium signaling pathway and axon guidance. The down-regulated hsa-miR-4657 and hsa-miR-342-3p might be associated with the development of ANE in pediatric patients with influenza by regulation of calcium pathways and axon guidance.