首页|Upregulation of E-cadherin by the combination of methionine restriction and HDAC2 intervention for inhibiting gastric carcinoma metastasis

Upregulation of E-cadherin by the combination of methionine restriction and HDAC2 intervention for inhibiting gastric carcinoma metastasis

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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.

methionine restrictionHDAC2gastric cancermetastasis

Yifan Li、Chenxi Liu、Lin Xin、Chuan Liu、Jiaqing Cao、Zhenqi Yue、Jie Sheng、Yiwu Yuan、Qi Zhou、Zhiyang Liu

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Department of General Surgery,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China

Excellent Ophthalmology Class 221,School of Ophthalmology & Optometry,Nanchang University,Nanchang 330006,China

Jiangxi Province Key Research and Development ProgramJiangxi Province Academic and Technical Leaders Training Program for Major Disciplines(Leading Talents Program)国家自然科学基金国家自然科学基金

20203BBG7305620213BCJ220148216047582360591

2024

10.3724/abbs.2023244

生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCD
影响因子：0.772
ISSN：1672-9145
年,卷(期)：2024.56(1)
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