Published on Aug. 25, 2018 in Biochem Biophys Res Commun volume 502(4).

PubMed ID: 29842885

DOI: S0006-291X(18)31252-X

Abstract:

N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification inmammalian mRNAs. Emerging evidences suggest that m(6)A modification is profoundlyimplicated in many biological processes, including cancer development. However,limited knowledge is available about the functional importance of m(6)A in lungcancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, wefirst identified fat mass- and obesity-associated protein (FTO) as a prognosticfactor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but notother m(6)A modification genes including METTL3, METTL14 and ALKBH5, was the majordysregulated factor responsible for aberrant m(6)A modification in LUSC.Loss-of-function studies suggested that FTO knockdown effectively inhibited cellproliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells.Furthermore, overexpression of FTO, but not its mutant form, facilitated themalignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expressionby reducing m(6)A levels and mRNA stability in MZF1 mRNA transcript, leading tooncogenic functions. Taken together, our study demonstrates the functionalimportance of FTO in the tumor progression of LUSC and provides a potentialtherapeutic target for LUSC treatment.CI - Copyright © 2018 Elsevier Inc. All rights reserved.