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. N 6 -methyladenosine modification in 3′-UTR of MYCN promoted its interaction with miR-98. The data collectively demonstrated that RNA m 6 A 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.

Neuronal extracellular vesicle derived miR-98 prevents salvageable neurons from microglial phagocytosis in acute ischemic stroke

“…MiR-98, as a member of let-7 group, has been reported to participated in several neurological diseases such as Alzheimer's Disease 42 , neuroblastoma 43 and neuroinflammatory conditions 17 . Whereas, the specific effects and mechanisms of miR-98 involved in the pathophysiological progress of ischemic stroke remain unknown.…”

Epitranscriptomics: A New Layer of microRNA Regulation in Cancer

“…Furthermore, a genome-wide analysis of m6A in glioma stem cells highlighted that m6A deposition on the 3 UTR of several mRNAs may affect their targeting by different miRNAs [199]. On the other hand, Cheng and colleagues [200] showed an effect at odds with this. Indeed, in neuroblastoma, m6A modification in N-Myc 3 UTR near a miR-98-binding site is necessary to promote the miR-98-mediated posttranscriptional repression of N-Myc.…”

m6A Modification in Mammalian Nervous System Development, Functions, Disorders, and Injuries

“…Knockdown of METTL3 suppresses aggressive and tumorigenic properties of GSCs by causing YTHDC1-dependent nonsense-mediated mRNA decay of SRSF , and subsequent decrease of SRSF protein level ( Li et al, 2019 ). m 6 A modification also regulates neuroblastoma, another common malignant brain tumor ( Cheng et al, 2020 ). MYCN is a genetic biomarker of high risk and poor outcome in neuroblastoma.…”

“…MYCN is a genetic biomarker of high risk and poor outcome in neuroblastoma. m 6 A modification in the 3′UTR of MYCN promotes its interaction with miR-98, decreasing MYCN expression and inhibiting neuroblastoma progression ( Cheng et al, 2020 ). These studies indicate that m 6 A modification could be a promising target for anti-brain tumor therapy.…”