Hepatoblastoma (HB) is one of the most common liver malignancies in children, while the molecular basis of the disease is largely unknown. Therefore, this study aims to explore the key genes and molecular mechanisms of the pathogenesis of HB using a bioinformatics approach. The gene expression dataset GSE131329 was used to find differentially expressed genes (DEGs). Functional and enrichment analyses of the DEGs were performed by the EnrichR. Then, the protein-protein interaction (PPI) network of the up-regulated genes was constructed and visualized using STRING database and Cytoscape software, respectively. MCODE was used to detect the significant modules of the PPI network, and cytoHubba was utilized to rank the important nodes (genes) of the PPI modules. Overall, six ranking methods were employed and the results were validated by the Oncopression database. Moreover, the upstream regulatory network and the miRNA-target interactions of the up-regulated DEGs were analyzed by the X2K web and the miRTarBase respectively. A total of 594 DEGs, including 221 up- and 373 down-regulated genes, were obtained, which were enriched in different cellular and metabolic processes, human diseases, and cancer. Furthermore, 15 hub genes were screened, out of which, 11 were validated. Top 10 transcription factors, kinases, and miRNAs were also determined. To the best of our knowledge, the association of RACGAP1, MKI67, FOXM1, SIN3A, miR-193b, and miR-760 with HB was reported for the first time. Our findings may be used to shed light on the underlying mechanisms of HB and provide new insights for better prognosis and therapeutic strategies.

肝母细胞瘤（HB）是儿童最常见的肝脏恶性肿瘤之一，但该疾病的分子基础在很大程度上尚不清楚。因此，本研究旨在利用生物信息学方法探讨HB发病的关键基因和分子机制。基因表达数据集 GSE131329 用于查找差异表达基因 (DEG)。DEG 的功能和富集分析由 EnrichR 进行。然后，分别使用STRING数据库和Cytoscape软件构建并可视化上调基因的蛋白质-蛋白质相互作用（PPI）网络。利用MCODE检测PPI网络的重要模块，利用cytoHubba对PPI模块的重要节点（基因）进行排序。总体而言，采用了六种排名方法，结果由 Oncopression 数据库进行了验证。此外，上调DEG的上游调控网络和miRNA-靶点相互作用分别通过X2K web和miRTarBase进行了分析。共获得594个DEG，包括221个上调基因和373个下调基因，富集于不同的细胞和代谢过程、人类疾病和癌症。此外，还筛选了 15 个枢纽基因，其中 11 个得到验证。还确定了前 10 个转录因子、激酶和 miRNA。据我们所知，首次报道了RACGAP1、MKI67、FOXM1、SIN3A、miR-193b和miR-760与HB的关联。我们的研究结果可用于阐明 HB 的潜在机制，并为更好的预后和治疗策略提供新的见解。