DYRK3 contributes to differentiation and hypoxic control in neuroblastoma

Neuroblastoma (NB), a pediatric cancer of the peripheral sympathetic nervous system, represents the most frequent solid malignancy in infants. Treatment of high-risk patients is still challenging and, depending on the genetic make-up and involved risk factors, the 5-year survival rate can drop to only 30%. Here, we found that the expression of the Dual Specificity Tyrosine Phosphorylation Regulated Kinase 3 (DYRK3) is increased in NB and is associated with decreased survival in NB patients. We further identified DYRK3 as a cytoplasmic kinase in NB cells and found that its levels are increased by hypoxic conditions. Further mechanistic studies revealed that DYRK3 acts as a negative regulator of HIF-driven transcriptional responses, suggesting that it functions in a negative feedback loop controlling the hypoxic response. Moreover, DYRK3 negatively impacted on NB cell differentiation, proposing an oncogenic role of this kinase in the etiology of NB. In summary, we describe novel functions of the DYRK3 kinase in NB, which will help to further improve the understanding of this disease eventually leading to the design of improved therapeutic concepts. •Expression of DYRK3 is increased in the pediatric malignancy neuroblastoma (NB).•DYRK3 expression is associated with decreased survival in NB patients.•DYRK3 protein levels are increased upon hypoxia in NB.•DYRK3 acts as a negative regulator of HIF-driven transcriptional responses, suggesting a functional negative feedback loop.•Finally, DYRK3 negatively impacted on NB cell differentiation, proposing an oncogenic role of this kinase in the etiology of NB.