Neuroblastoma (NB) is a prevalent pediatric tumor, accounting for over 15% of cancer-related fatalities in children. Super-enhancers (SEs), as pivotal cis-regulatory elements known for driving oncogene expression across various tumors, may serve as an innovative strategy for deciphering NB pathogenesis. Here, we meticulously analyzed epigenomic and transcriptomic data to delineate the distinct SE landscape in NB. Our study identified a NB-specific and NB-common SE at the MAB21L2 locus. Functional analyses further underlined MAB21L2's oncogenic role in NB, linking its high expression to poor patient outcomes. MAB21L2 knockdown strikingly inhibited the growth of NB tumor cells in vitro and reduced their proliferation in vivo. Notably, through RNA-seq analysis and experimental verification, we demonstrated that MAB21L2 substantially enhanced the migratory capacity of NB cells. Collectively, these findings underscore the indispensable role of the super-enhancer-MAB21L2 axis in the pathogenesis of NB and provide mechanistic insights into NB progression.

Investigate the function of glutathione reductase-associated protein 5 (GLRX5) and its prognostic significance, as well as its association with CAFs and the TME. Based on data from TCGA and the GEO databases, this study investigates the expression of GLRX5 in BLCA and its association with clinical outcomes. Using the ssGSEA algorithm, we explored the association between functional features of GLRX5 and BLCA. We validated our findings using in vitro cellular functional assays. We explored the regulatory mechanisms associated with GLRX5 using GO, KEGG, and GSEA. Furthermore, based on single-cell and spatial transcriptomics data from bladder cancer, we analyzed the expression patterns and potential functions of GLRX5 in bladder cancer. The results of the above analyses were experimentally explored and validated. High expression of GLRX5 in BLCA correlates with malignant biological behavior and poor prognosis. Enrichment analysis indicates that GLRX5 is primarily associated with malignant functional characteristics in bladder cancer, and its expression levels are also linked to EMT, OXPHOS, and FAM. The above analyses have all been validated through in vitro experiments. Single-cell and spatial transcriptomics analyses indicate that GLRX5 is also expressed in CAFs and participates in metabolic pathways. Experiments demonstrated that GLRX5 promotes the activation of CAFs and may enhance tumor cell migration by influencing pathways within the TME. High expression of GLRX5 in tumor cells promotes malignant biological behavior and predicts poor prognosis. At the same time, high expression of GLRX5 in CAFs promotes tumor cell migration by affecting the TME.