摘要
BACKGROUND Helicobacter pylori(H.pylori)colonizes the human gastric mucosa and is implicated in the development of gastric cancer(GC).The tumor microenvironment is characterized by hypoxia,where hypoxia-inducible factor-1α(HIF-1α)plays a key role as a transcription factor,but the mechanisms underlying H.pylori-induced HIF-1αexpression and carcinogenesis remain unclear.AIM To explore the underlying mechanism of H.pylori-induced HIF-1αexpression in promoting the malignant biological behavior of gastric epithelial cells(GES-1).METHODS The study was conducted with human GES-1 cells in vitro.Relative protein levels of methyltransferase-like protein 14(METTL14),HIF-1α,main proteins of the PI3K/AKT pathway,epithelial-mesenchymal transition(EMT)biomarkers,and invasion indicators were detected by Western blot.Relative mRNA levels of METTL14 and HIF-1αwere detected by quantitative reverse transcription-polymerase chain reaction.mRNA stability was evaluated using actinomycin D,and the interaction between METTL14 and HIF-1αwas confirmed by immunofluorescence staining.Cell proliferation and migration were evaluated by cell counting kit-8 assay and wound healing assay,respectively.RESULTS H.pylori promoted HIF-1αexpression and activated the PI3K/AKT pathway.Notably,METTL14 was downregulated in H.pylori-infected gastric mucosal epithelial cells and positively regulated HIF-1αexpression.Functional experiments showed that the overexpression of HIF-1αor knockdown of METTL14 enhanced the activity of the PI3K/AKT pathway,thereby driving a series of malignant transformation,such as EMT and cell proliferation,migration,and invasion.By contrast,the knockdown of HIF-1αor overexpression of METTL14 had an opposite effect.CONCLUSION H.pylori-induced underexpression of METTL14 promotes the translation of HIF-1αand accelerates tumor progression by activating the PI3K/AKT pathway.These results provide novel insights into the carcinogenesis of GC.
基金
Supported by The Key Research and Development and Promotion Special Project of Henan Province,No.222102310069
National Natural Science Foundation of China,No.82073618.
