Identification of miRNAs Associated with Infantile-Onset Pompe Disease

鉴定与婴儿型庞贝病相关的miRNA

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Abstract

INTRODUCTION: Infantile-onset Pompe disease (IOPD), which presents with a broad spectrum of nonspecific findings in newborns and lacks a clearly defined clinical picture, is a significant factor that delays patients' access to diagnosis and treatment. In this disease, insufficient diagnosis rates, low levels of clinical suspicion, and delays in diagnosis are the main problems that hinder early and accurate diagnosis. This study aims to address diagnostic and therapeutic challenges by elucidating the functional roles and associations of microRNAs (miRNAs) in the pathogenesis of IOPD. As a result of comparative data analysis, an inventory of known and novel miRNA sequences predicted to target pathogenic pathways associated with IOPD was established. METHODS: In this study, IOPD and control samples from GSE38680 data were normalized on the Affymetrix platform. Differential gene expression analysis was performed using the limma package, and common differentially expressed (DEGs) were identified. Subsequently, significant signaling pathways were identified using WebGestalt and Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) databases, and the false discovery rate (FDR) correction was applied. Finally, miRNA expression analysis and miRNA interactions associated with IOPD genes were examined using R packages such as miRNATap and multiMiR. RESULTS: In this study, 1,967 DEGs (1,108 upregulated, 859 downregulated) were identified in the GSE38680 data. GO and KEGG analyses revealed biological processes associated with IOPD, particularly muscle function and the lysosome pathway. In the analysis of miRNAs associated with the DEGs, 10 miRNAs were predicted to bind directly to the 3'-untranslated region (UTR) of the GAA gene. CONCLUSION: Early diagnosis is critical to prevent or mitigate irreversible organ damage associated with the progression of IOPD, and circulating miRNAs may serve as additional biomarkers for diagnosis, disease severity, and treatment response. This study used high-throughput technology to identify potential miRNAs for IOPD.

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