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KDM5B expression in cisplatin resistant neuroblastoma cell lines
Marie Belhajova1, Natalia Podhorska1, Ales Vicha1
1Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, 15006 Prague, Czech Republic.
Abstract:
Chemoresistance is a major problem in successful cancer therapy. Lysine-specific demethylase 5B (KDM5B), is a member of the KDM5 family of histone demethylases, whose dysregulation has been observed in numerous types of cancer and plays a role in drug tolerance. The present study examined KDM5B expression in high risk neuroblastoma cell lines. Its level was markedly reduced in cisplatin-resistant cells, UKF-NB-4CDDP, compared with parental sensitive cells UKF-NB-4. Moreover, KDM5B-silencing did not affect either viability nor the response to CDDP in resistant cells, and led to increase of proliferation and migration in CDDP resistant cells but not in sensitive ones. Compliant with these results, short interfering KDM5B transfection resulted in increased S phase in resistant cells. Overall, these findings suggested that KDM5B may be involved in the survival mechanisms of neuroblastoma cells, which makes KDM5B a promising factor for the prediction of sensitivity to CDDP that should therefore be considered for future research.
Insights
Lysine-specific demethylase 5B (KDM5B) is reduced in cisplatin-resistant neuroblastoma cells. Lower KDM5B levels correlate with increased cell proliferation and migration, suggesting KDM5B predicts chemoresistance.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Chemoresistance poses a significant challenge in effective cancer therapy.
- Lysine-specific demethylase 5B (KDM5B), a histone demethylase, is implicated in cancer dysregulation and drug tolerance.
- KDM5B's role in neuroblastoma chemoresistance requires further investigation.
Purpose of the Study:
- To investigate KDM5B expression in high-risk neuroblastoma cell lines.
- To determine the functional role of KDM5B in cisplatin resistance in neuroblastoma.
Main Methods:
- Analysis of KDM5B expression levels in cisplatin-sensitive and resistant neuroblastoma cell lines.
- KDM5B gene silencing using short interfering RNA (siRNA).
- Assessment of cell viability, proliferation, migration, and cell cycle phase distribution.
Main Results:
- KDM5B expression was significantly reduced in cisplatin-resistant neuroblastoma cells (UKF-NB-4CDDP) compared to sensitive cells (UKF-NB-4).
- Silencing KDM5B in resistant cells did not affect viability or cisplatin response but increased proliferation and migration.
- KDM5B knockdown led to an increased S phase population in resistant cells.
Conclusions:
- KDM5B appears to be involved in the survival mechanisms of neuroblastoma cells.
- Reduced KDM5B expression may predict sensitivity to cisplatin treatment.
- KDM5B is a potential biomarker for predicting chemoresistance in neuroblastoma.
