FOXJ3, a novel tumor suppressor in neuroblastoma.

Neuroblastoma (NB) poses a significant challenge in pediatric cancer care due to its aggressive nature and poor prognosis. While advances have been made in clinical treatments, therapy resistance remains a tough hurdle in NB treatment. While much research has focused on identifying oncogenes in NB, there has been less emphasis on understanding tumor suppressors. This study aimed to discover a new transcription factor that could address patient stage, risk level, and MYCN amplification status while exhibiting tumor-suppressive properties in NB patients. Using advanced bioinformatics techniques, we identified unique transcription factor signature that corresponded to patient characteristics. By analyzing regulon specificity scores, we prioritized Forkhead Box J3 (FOXJ3) as a potential novel driver transcription factor with tumor-suppressive functions in NB. Validation experiments on NB patients and patient-derived xenograft (PDX) tumors confirmed higher FOXJ3 expression in low-risk versus high-risk patients and in PDXs from diagnostic tumors versus relapse-specific tumors. Notably, the overexpression of FOXJ3 was associated with reduced cell density, proliferation, cells in S phase, colony-formation ability, transwell migration, neurosphere formation, spheroid diameter, and inhibition of AKT signaling in NB cells. Overall, these findings suggest that FOXJ3 functions as a novel tumor suppressor in NB, holding promise for potential therapeutic interventions.