The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through the regulation of JUNB.
Cell Line, Tumor
Epithelial-Mesenchymal Transition
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Knockdown Techniques
Humans
Lung Neoplasms
/ genetics
Methyltransferases
/ genetics
Phenotype
RNA Stability
/ drug effects
Transcription Factors
/ genetics
Transforming Growth Factor beta
/ pharmacology
Epithelial-mesenchymal transition
JUNB
Lung cancer
METTL3
RNA methylation
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
26 03 2020
26 03 2020
Historique:
received:
06
12
2019
revised:
06
01
2020
accepted:
07
01
2020
pubmed:
27
1
2020
medline:
24
9
2020
entrez:
27
1
2020
Statut:
ppublish
Résumé
N6-Methyladenosine (m6A) is the most common internal chemical modification of mRNAs involved in many pathological processes including various cancers. In this study, we investigated the role of m6A methyltransferase METTL3 in TGF-β-induced epithelial-mesenchymal transition (EMT) of lung cancer cell lines. The expression of METTL3 and m6A RNA modification were increased during TGF-β-induced EMT of A549 and LC2/ad lung cancer cells. Knockdown of METTL3 inhibited TGF-β-induced morphological conversion of the cells, enhanced cell migration potential and the expression changes of EMT-related marker genes such as CDH1/E-cadherin, FN1/Fibronectin and VIM/Vimentin. Mechanistic investigations revealed that METTL3 knockdown decreased the m6A modification, total mRNA level and mRNA stability of JUNB, one of the important transcriptional regulators of EMT. Over-expression of JUNB partially rescued the inhibitory effects of METTL3 knockdown in the EMT phenotypes. This study demonstrates that m6A methyltransferase METTL3 is indispensable for TGF-β-induced EMT of lung cancer cells through the regulation of JUNB.
Identifiants
pubmed: 31982139
pii: S0006-291X(20)30105-4
doi: 10.1016/j.bbrc.2020.01.042
pii:
doi:
Substances chimiques
JunB protein, human
0
Transcription Factors
0
Transforming Growth Factor beta
0
Methyltransferases
EC 2.1.1.-
METTL3 protein, human
EC 2.1.1.62
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
150-155Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest None.