Ferroptosis regulator NOS2 is closely associated with the prognosis and cell malignant behaviors of hepatoblastoma: a bioinformatic and in vitro study

Background Hepatoblastoma (HB) is the most common liver tumor in children with easy metastasis. The emergence of ferroptosis as a novel form cell death has gained increased attention various human cancers. However, roles ferroptosis-related (FR) genes HB remain elusive Methods GSE133039, GSE131329, and GSE81928 datasets were utilized for screening core FR HB. Through Lasso regression analysis using support vector machine recursive feature elimination (SVM-RFE) algorithm, three candidate obtained characterizing Their expression patterns their clinical associations explored through ‘Limma’ R package, diagnostic potential was evaluated ROC curves. Nitric oxide synthase 2 (NOS2) emerged further analyses. CIBERSORT algorithm GSEA dataset used to respectively investigate immune metabolism effects NOS2; former validated immunofluorescence. GSDC database employed analyze correlation between NOS2 therapeutic efficacy multiple drugs. PCR, Western blotting, colony formation assays, Transwell experiments, determine biological functions cells. Potential upstream transcription factors predicted TRRUST, hTFtarget, GeneCards, JASPAR databases. Results NQO1, SLC1A4, identified found be significantly upregulated samples. Nevertheless, only closely associated clinicopathological characteristics; high indicated poor prognosis, metastatic tendency, late stage. Immune analyses that concomitant decreased infiltration levels CD8+ T cells but macrophages. revealed failed affect enrichments glycolysis, fatty acid metabolism, cholesterol biosynthesis Moreover, positively correlated IC 50 values trametinib, lapatinib, cisplatin. overexpression promoted proliferation, migration invasion HepG2 HuH-6 JUND transcriptional regulator by binding its promoter (5’-TTCTGACTCTTTT-3’). Conclusion plays significant role assessments holds promise target.