RUNX1 and RUNX3 are master transcription factors in sensory neuron lineage specifications. Protein levels of such developmental regulators are tightly controlled during carcinogenesis, in order to block differentiation and drive proliferation. Here we report that neuroblastoma specific microRNAs inhibit protein syntheses of RUNX1 and RUNX3 through 3’UTR sequences. Computational prediction identified two putative binding sequences for N-Myc-activated microRNAs both in RUNX1 and RUNX3 3’UTRs. Streptavidin RNA aptamer-tagged 3’UTR sequences pulled down miR-17, miR-18a, miR-19a, miR-20a or miR-130a from neuroblastoma cell lysate. 3’UTR target protection from N-Myc-activated microRNAs increased protein synthesis of RUNX1 or RUNX3 and induced differentiation in neuroblastoma cell lines. Together, protein levels of RUNX1 and RUNX3 are post-transcriptionally regulated by N-Myc-activated microRNAs, highlighting the mutual negative feedback between N-Myc oncogene and RUNX3 tumor suppressor in neuroblastoma
