Abstract
Invasion and metastasis are the leading causes of death in individuals with malignant tumors,including gastric cancer.In this study,we aim to explore the effect and related mechanisms of methionine restriction(MR)on gastric carcinoma metastasis.In the MR cell model,gastric carcinoma cells are cultured in the MR medium,and in the animal model,BALB/c nude rodents are administered with a methionine-free diet after receiving injections of MKN45 cells into the caudal vein.Transwell assay is used to detect cell invasion and migration.Chromatin im-munoprecipitation is performed to investigate the levels of H3K9me2,H3K27Ac,and H3K27me3 in the E-cadherin promoter.The results show that MR inhibits gastric carcinoma cell migration,invasion,and lung metastasis.MR increases E-cadherin while reducing the H3K27me3 level in the E-cadherin promoter.E-cadherin expression in gastric carcinoma cells is adversely regulated by HDAC2.Overexpressing HDAC2 reduces the H3K27Ac level in the E-cadherin promoter,while interfering with HDAC2 increases the H3K27Ac level.HDAC2 interference under MR conditions further upregulates E-cadherin expression and inhibits gastric carcinoma cell migration,invasion,and lung metastasis.MR combined with HDAC2 interference promotes E-cadherin expression by mediating the me-thylation and acetylation of E-cadherin,thus inhibiting the invasion,migration,and lung metastasis of gastric carcinoma cells.Our study provides a new theoretical basis for the inhibitory effect of MR on gastric cancer.
基金项目
Jiangxi Province Key Research and Development Program(20203BBG73056)
Jiangxi Province Academic and Technical Leaders Training Program for Major Disciplines(Leading Talents Program)(20213BCJ22014)
国家自然科学基金(82160475)
国家自然科学基金(82360591)
国家科技期刊平台
NSTL
万方数据