Related Experiment Video
Updated: Jun 2, 2025
Zebrafish Model of Neuroblastoma Metastasis
Published on: March 14, 2021
FOXJ3, a novel tumor suppressor in neuroblastoma
Kishore B Challagundla1,2,3, Anup S Pathania2, Haritha Chava4
1School of Interdisciplinary Informatics, University of Nebraska Omaha, 1110 South 67th Street, Omaha, NE 68182, USA.
Abstract:
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.
Insights
Researchers identified Forkhead Box J3 (FOXJ3) as a novel tumor suppressor in neuroblastoma (NB). Higher FOXJ3 levels correlate with better patient outcomes and reduced tumor growth, offering potential new therapeutic targets.
Area of Science:
- Pediatric Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Neuroblastoma (NB) is a challenging pediatric cancer with poor prognosis, often complicated by therapy resistance.
- Research has primarily focused on oncogenes, with less attention paid to crucial tumor suppressor genes in NB.
- Identifying novel tumor suppressors is vital for developing more effective NB treatments.
Purpose of the Study:
- To discover a novel transcription factor with tumor-suppressive properties in neuroblastoma.
- To identify a factor that correlates with patient stage, risk level, and MYCN amplification status.
- To investigate the potential of Forkhead Box J3 (FOXJ3) as a therapeutic target in NB.
Main Methods:
- Utilized advanced bioinformatics to identify transcription factor signatures associated with NB patient characteristics.
- Analyzed regulon specificity scores to prioritize candidate tumor suppressors.
- Conducted validation experiments on NB patient samples and patient-derived xenograft (PDX) models.
- Assessed the functional impact of FOXJ3 overexpression on NB cell behavior and signaling pathways.
Main Results:
- Identified a unique transcription factor signature linked to NB patient profiles.
- Prioritized Forkhead Box J3 (FOXJ3) as a potential tumor suppressor based on bioinformatics analysis.
- Confirmed higher FOXJ3 expression in low-risk vs. high-risk NB patients and diagnostic vs. relapse tumors.
- Demonstrated that FOXJ3 overexpression reduces NB cell proliferation, migration, and neurosphere formation, while inhibiting AKT signaling.
Conclusions:
- Forkhead Box J3 (FOXJ3) functions as a novel tumor suppressor in neuroblastoma.
- FOXJ3 expression levels are inversely correlated with NB risk and progression.
- FOXJ3 represents a promising candidate for future therapeutic strategies in neuroblastoma treatment.
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