TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000281043
  • Gene Name:MYCN
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:neuroblastoma
  • Tissue:NB-1643, LA1-5S, LA1-55N and IMR32,SK-N-SH, SK-N-F1, SK-NAS and SHEP1

Other information

  • Title:Targeting MYCN IRES in MYCN-amplified neuroblastoma with miR-375 inhibits tumor growth and sensitizes tumor cells to radiation.
  • Journal:Mol Oncol
  • Published:2015
  • PubMed ID:25864587
  • Abstract:The MYCN oncogene is amplified in 20% of neuroblastomas, leading to its overexpression at both the mRNA and protein levels. MYCN overexpression is strongly associated with advanced disease stage, rapid tumor progression and a worse prognosis. In the present study, we identified microRNA-375 (miR-375) as a negative regulator of MYCN: enforced expression of miR-375 inhibited MYCN-amplified neuroblastoma in vitro and in vivo. Upon searching the website miRbase for possible miR-375 binding sites within the whole MYCN mRNA, we found that the MYCN 5＇-UTR had significant sequence complementarity to miR-375, yet no complementary sequences existed within the MYCN 3＇-UTR and coding regions. Enforced overexpression of miR-375 efficiently inhibited MYCN mRNA translation and protein synthesis, via an IRES-dependent mechanism. In athymic nude mouse model with human MYCN-amplified neuroblastoma, MYCN downregulation by miR-375 led to inhibition of tumor cell growth and tumorigenicity. In particular, miR-375-regulated inhibition of MYCN translation was enhanced when MYCN-amplified neuroblastoma cells were exposed to stress stimulation, such as ionizing irradiation (IR), resulting in a remarkable increase in the neuroblastoma＇s sensitivity to IR-induced cell death. Our results identified a novel mechanism by which IRES-dependent translation of MYCN is repressed by miR-375, particularly during cellular stress, highlighting a potential anticancer strategy: the development of miR-375 as a novel therapeutic agent to treat MYCN-amplified neuroblastoma.
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