Jumonji domain-containing 6 promotes the expansion of neuroblastoma stem cells by activating the wingless/ integrated pathway

Objective: Cancer stem cells are involved in chemotherapy resistance. Neuroblastoma (NB) is a common solid tumor in children, which is responsible for about 15% of pediatric cancer deaths. Jumonji domain-containing 6 (JMJD6), which is an arginine demethylase and lysine hydroxylase, regulates the progression of various tumors. However, the molecular mechanism underlying JMJD6’s activity in NB stem cells remains unclear. Thus, this study aims to explore the role of JMJD6 in NB stem cells. Material and Methods: Side population and sphere formation assays were used to investigate the role of JMJD6 in NB stem cell expansion. Immunohistochemistry was performed to determine the expression level of JMJD6 in NB tissues. Luciferase reporter assays were used to discover the effect of JMJD6 on the wingless/integrated (WNT) pathway. Results: JMJD6 was upregulated in NB tissues and cells ( P < 0.05). NB patients with high JMJD6 levels had poor outcomes. JMJD6 could serve as an independent prognostic factor for NB. JMJD6 overexpression promoted NB stem cell expansion, whereas JMJD6 knockdown had the opposite effect, as determined by cell and animal models. Mechanism Roche studies showed that JMJD6 promoted NB stem cell expansion by activating the WNT pathway. Conclusion: JMJD6 promotes NB stem cell expansion by activating the WNT pathway, thereby providing a new target for NB therapy and a prognostic factor for patients with NB.