RRC ID 58730
Author Wanna-Udom S, Terashima M, Lyu H, Ishimura A, Takino T, Sakari M, Tsukahara T, Suzuki T.
Title The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through the regulation of JUNB.
Journal Biochem Biophys Res Commun
Abstract 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.
Volume 524(1)
Pages 150-155
Published 2020-3-26
DOI 10.1016/j.bbrc.2020.01.042
PII S0006-291X(20)30105-4
PMID 31982139
MeSH Cell Line, Tumor Epithelial-Mesenchymal Transition / drug effects* Epithelial-Mesenchymal Transition / genetics Gene Expression Regulation, Neoplastic / drug effects Gene Knockdown Techniques Humans Lung Neoplasms / genetics Lung Neoplasms / metabolism* Lung Neoplasms / pathology* Methyltransferases / genetics Methyltransferases / metabolism* Phenotype RNA Stability / drug effects Transcription Factors / genetics Transcription Factors / metabolism* Transforming Growth Factor beta / pharmacology*
IF 2.985
Times Cited 5
Human and Animal Cells LC-2/ad(RCB0440) A549