Integrated miRNA-Target Gene Analysis Reveals Complementary Molecular Biomarkers and Regulatory Networks in Pediatric...

Neuroblastoma is a heterogeneous pediatric malignancy with marked molecular diversity and variable clinical behavior. Although current risk stratification incorporates clinical and genomic factors, additional biomarkers are needed to improve tumor characterization and advance precision oncology. The present study investigated the expression of miR-141-3p, miR-150-5p, miR-181a-5p, and miR-182-5p and their predicted target genes in pediatric neuroblastoma. Tumor samples from 58 neuroblastoma and 13 ganglioneuroma patients were compared with 41 adjacent non-tumor tissues, while an independent cohort of 17 frozen tumors (13 neuroblastomas and 4 ganglioneuroblastomas) was used for integrated miRNA-target gene analyses. Diagnostic performance, functional enrichment, integrated analyses, and clinicopathological associations were evaluated. All four miRNAs were predominantly downregulated in tumors, with miR-150-5p and miR-181a-5p showing the most consistent reduction. A combined panel of miR-141-3p, miR-150-5p, and miR-181a-5p discriminated tumor from adjacent non-tumor tissues with 80.7% accuracy. miR-141-3p and miR-150-5p were associated with age at diagnosis, and miR-181a-5p was associated with overall survival. Functional enrichment implicated these miRNAs in neural crest development, stemness, neuronal differentiation, and major oncogenic pathways. Integrated analyses revealed reduced BCL2 expression in high-risk tumors and a positive correlation between miR-181a-5p and MYCN. These findings support these miRNAs as complementary molecular biomarkers and provide insights into miRNA-mediated regulatory networks in neuroblastoma.