Abstract：
:Aberrant methylation of promoter CpG islands (CGIs) can inactivate the expression of many tumor suppressor genes and play an important role in the carcinogenesis of gastric cancer. The tumor suppressor gene RB1, which encodes a cell cycle regulator, is hypermethylated and downregulated in multiple kinds of cancer. Activation of RB1 expression through DNA demethylation is a potential strategy for the treatment of gastric cancer. Herein, we found that the methylation status of the RB1 promoter was negatively related to the development of gastric tumors, while its expression was positively correlated with TET2 and TET3 expression. Further reactivation of RB1 expression by curcumin could inhibit gastric cell viability and carcinogenesis both in vitro and in vivo. Molecular docking and other studies confirmed that curcumin could bind to and upregulate the expression of TET2 and TET3 with hydrogen bonds and arene-H bonds, suggesting that demethylation of RB1 was attributed to reactivation of the demethylation enzymes TET2 and TET3 after curcumin treatment. Thus, our findings reveal a promising therapeutic strategy for gastric cancer prevention and treatment through RB1 demethylation and reactivation.
journal_name
Life Scijournal_title
Life sciencesauthors
Cao D,Jia Z,Wu Y,Su T,Zhao D,Wu M,Tsukamoto T,Oshima M,Jiang J,Cao Xdoi
10.1016/j.lfs.2020.118580subject
Has Abstractpub_date
2020-12-15 00:00:00pages
118580eissn
0024-3205issn
1879-0631pii
S0024-3205(20)31333-3journal_volume
263pub_type
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