Year: 2026
Type: article
Abstract: Chemoresistance is a major cause of cancer therapy failure.Increasing evidence points to the importance of histone lysine demethylase function, whose dysregulation has been described in several types of cancer.KDM5, a family of histone lysine demethylases, may carry out a key role in the downregulation of tumor-suppressors or upregulation of oncogenes and in the development of drug tolerance.The present study examined the expression of KDM5D in cell lines derived from high-risk neuroblastoma.The present study found that KDM5D expression was lost in all cisplatin-chemoresistant neuroblastoma cell lines compared with sensitive parental cells.In addition, the cisplatin-chemoresistant neuroblastoma cell line had increased expression of the ubiquitin ligase cullinaA 4A (CUL4A) compared with the sensitive parental cells.CUL4A carries out a role in cellular processes and its aberrant regulation has been observed in a number of types of cancer.The present study shows that silencing of KDM5D causes a more aggressive phenotype of neuroblastoma by promoting cell proliferation and migration, evading cell death, promoting S phase of the cell cycle and desensitizing sensitive cells to cisplatin via the gene CUL4A.In addition, ectopic expression of KMD5D in a cisplatin-resistant cell line reversed these phenomena.The results suggest that KDM5D and/or CUL4A may be a biomarkers of chemoresistance to cisplatin and a potential therapeutic target in neuroblastoma.
Source: Oncology Reports
DOI: 10.3892/or.2026.9084
Institutions: Charles University, University Hospital in Motol
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Award: G6769690202
OpenAlex ID: W7131362841
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