Published on March 14, 2017 in Cell Rep volume 18(11).

PubMed ID: 28297667

DOI: 10.1016/j.celrep.2017.02.059

Abstract:

RNA modifications play critical roles in important biological processes. However,the functions of N(6)-methyladenosine (m(6)A) mRNA modification in cancer biologyand cancer stem cells remain largely unknown. Here, we show that m(6)A mRNAmodification is critical for glioblastoma stem cell (GSC) self-renewal andtumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNAmethyltransferase complex, dramatically promotes human GSC growth, self-renewal, andtumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNAdemethylase FTO suppresses GSC growth and self-renewal. Moreover, inhibition of FTOsuppresses tumor progression and prolongs lifespan of GSC-grafted micesubstantially. m(6)A sequencing reveals that knockdown of METTL3 or METTL14 inducedchanges in mRNA m(6)A enrichment and altered mRNA expression of genes (e.g., ADAM19)with critical biological functions in GSCs. In summary, this study identifies them(6)A mRNA methylation machinery as promising therapeutic targets for glioblastoma.CI - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.