RNA N6-methyladenosine modification is required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression

Abstract

Neuroblastoma (NB) is one of the most common malignant tumors of the sympathetic nervous system in childhood. NB severely threatens patient’s health and life. However, more effective diagnosis and treatment methods are badly needed in clinics all over the world. MYCN is well recognized as a genetic biomarker of high risk and poor outcome in NB. miRNAs are small RNAs and miR-98 involved in the pathogenesis of various cancers. The role and mechanism of miR-98 in NB remains to be investigated. Here we found that miR-98 was decreased in human MYCN-high-expression NB tissues, and its down-regulation was associated with poor prognosis of NB. Over-expression of miR-98 inhibited cell proliferation, migration and invasion of NB cells. The analysis by employing the software of miRanda predicted the possible binding sites of miR-98 in the 3′-UTR of MYCN, and experimental data illustrated that miR-98 directly bound to MYCN 3′-UTR and decreased MYCN expression. Over-expression of MYCN rescued the decreased malignant phenotype caused by over-expression of miR-98 in NB. N6-methyladenosine modification in 3′-UTR of MYCN promoted its interaction with miR-98. The data collectively demonstrated that RNA m6A modification was required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression, and miR-98 might be novel targets for NB detection and treatment.