MYCN Gene Is Activated by High-Level Expression of Stress-Inducible Isoform of Oct-1 Transcription Factor in Human...

MYCN is expressed in the developing nervous system and is vital for proliferation, migration, and homeostasis of differentiating neuronal cells. Its expression decreases during neuronal differentiation. A high level of MYCN expression in neuroblastoma cells is a negative prognostic marker, and MYCN inhibition provides an efficient means to prevent tumor growth. Understanding MYCN regulation at the transcriptional level can help identify the regulatory pathways that may be targeted to reduce MYCN expression. The regulatory region of the MYCN gene was shown to contain binding sites for the transcription factor Oct-1 (POU2F1). Several Oct-1 isoforms present in IMR32 neuroblastoma cells were tested for effect on MICN expression, and only the primate-specific, stress-inducible isoform Oct-1Z was found to regulate MYCN in IMR32 cells during neuronal differentiation. High-level expression of Oct-1Z increased expression of MYCN and its target gene NEUROD1. Oct-1Z was thus identified as an activator of MYCN expression and a potential target for neuroblastoma therapy in patients with high levels of MYCN.