Identification and characterisation of STMN4 and ROBO2 gene involvement in neuroblastoma cell differentiation

To better understand neuroblastoma differentiation, we used microarray analysis to identify common gene expression changes from three differentiation models. This revealed STMN4 and ROBO2 to be consistently up-regulated in differentiated neuroblastoma cells induced by chromosome 1 transfer, MYCN knockdown, and 9-cis retinoic acid (9cRA). Furthermore, stable expression of transfected STMN4 or ROBO2 induced differentiation in IMR-32 cells. STMN4 and ROBO2 expression also increased in other 9cRA-induced differentiated neuroblastoma cell lines. Of clinical importance is that neuroblastoma patients with higher tumour mRNA expression of STMN4 and ROBO2 had better progression-free survival. This study highlights the importance of STMN4 and ROBO2 during neuroblastoma differentiation.

► STMN4 and ROBO2 gene expression is consistently up-regulated in neuroblastoma cells induced to differentiate. ► Ectopic expression of transfected STMN4 or ROBO2 induces IMR-32 cells to differentiate, showing a causal link with the differentiated phenotype. ► High tumour STMN4 and ROBO2 mRNA expression is associated with better progression-free survival of neuroblastoma patients.