METTL3-mediated m6A Modification of PDK1 mRNA Improves Lung Epithelial Cell Proliferation via Akt/mTOR Signaling
10.13865/j.cnki.cjbmb.2024.06.1035
- VernacularTitle:METTL3介导的PDK1 mRNA m6A修饰通过Akt/mTOR信号通路促进肺上皮细胞增殖
- Author:
Ai JIN
1
;
Meng-Yu LI
;
Qing-Zhu SUN
Author Information
1. 山西医科大学公共卫生学院营养与食品卫生学教研室,太原 030001;山西医科大学营养与食品科学研究所,太原 030001;山西医科大学煤炭环境致病与防治教育部重点实验室,太原 030001;山西医科大学黄河流域生态公共卫生安全研究中心
- Keywords:
methyltransferase 3(METTL3);
RNA m6A modification;
cell proliferation;
lung epithelial cells;
phosphate inositol dependent protein kinase-1(PDK1)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(7):934-946
- CountryChina
- Language:Chinese
-
Abstract:
Adenosine N6-methylation(m6A)has been shown to be associated with the cell proliferation.The role of RNA methyltransferase 3(METTL3),a key enzyme catalyzing m6A,in mediating m6A modification in lung epi-thelial cell proliferation remains unclear.This study aims to explore the effects and mechanisms of METTL3-media-ted m6A modification in regulating lung epithelial cell proliferation.Results showed that knockdown of METTL3 sig-nificantly inhibited cell growth in lung epithelial cells,while overexpression of METTL3 promoted cell proliferation(P＜0.05).Further Western blotting results demonstrated that the expression levels of the key proteins PCNA in-volved in cell growth and proliferation were significantly downregulated in METTL3 knockdown lung epithelial cells,along with a significant decrease in phosphorylation levels of Akt and mTOR(P＜0.05).Immunofluorescence stai-ning revealed a significant decrease in m6A modification levels in METTL3 knockdown lung epithelial cells(P＜0.05).Real-time quantitative PCR and Western blotting results indicated that the mRNA and protein expression levels of PDK1,an upstream regulator of the Akt-mTOR signaling pathway,were significantly decreased in MET-TL3 knockdown lung epithelial cells(P＜0.05).Mechanistically,m6A-IP-qPCR and RIP-qPCR results further demonstrated that METTL3 catalyzed m6A modification in the 3'UTR region of PDK1 mRNA,which was then rec-ognized by YTH N6-methyladenosine RNA-binding protein 1(YTHDF1),enhancing the stability of its mRNA.In conclusion,this study reveals that METTL3 promotes cell proliferation by enhancing PDK1 m6 A modification,thereby activating the Akt-mTOR signaling pathway.It provides evidence for a novel role of METTL3 in epithelial cell proliferation and offers new therapeutic targets for lung epithelial cell injury repair.
