KDM5D expression is lost in cisplatin‑resistant neuroblastoma cells

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.

KDM5D; chemoresistance; cisplatin; cullin 4A; neuroblastoma.