ReferenceID 2869

Sinomenine increases the methylation level at specific GCG site in mPGES-1 promoter to facilitate its specific inhibitory effect on mPGES-1

Biochim Biophys Acta Gene Regul Mech

Prostaglandin E 2 (PGE 2 ) in cancer and inflammatory diseases is a key mediator of disease progression. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to inhibit the expression of PGE 2 by depressing cyc

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Reference Id
2869
Evidence Id
19459
Core Evidence Id
19459
Source Reference Id
5723
Herb2 Reference Id
HBREF006520
Subject Paper Key
HBIN044111_35417776
Pubmed Id
35417776
Doi
10.1016/j.bbagrm.2022.194813
Paper Title
Sinomenine increases the methylation level at specific GCG site in mPGES-1 promoter to facilitate its specific inhibitory effect on mPGES-1
Paper Abstract
Prostaglandin E 2 (PGE 2 ) in cancer and inflammatory diseases is a key mediator of disease progression. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to inhibit the expression of PGE 2 by depressing cyclooxygenase (COX) in inflammatory treatments. However, the inhibition to COXs may cause serious side effects. Thus, it is urgent to develop new anti-inflammatory drugs aiming new targets to inhibit PGE 2 production. Microsomal prostaglandin E synthase 1 (mPGES-1) catalyzes the final step of PGE 2 biosynthesis. Therefore, the selective inhibition of mPGES-1 has become a promising strategy in the treatments of cancer and inflammatory diseases. Our previous studies confirmed that sinomenine (SIN) is a specific mPGES-1 inhibitor. However, the exact mechanism by which SIN inhibits mPGES-1 remains unknown. This study aimed to explain the regulation effect of SIN to mPGES-1 gene expression by its DNA methylation induction effect. We found that the demethylating agent 5-azacytidine (5-AzaC) reversed the inhibitory effect of SIN to mPGES-1. Besides, SIN selectively increased the methylation level of the promoter region in the mPGES-1 gene while the pretreatment of 5-AzaC suppressed this effect. The results also shows that pretreatment with SIN increased the methylation level of specific GCG sites in the promoter region of mPGES-1. This specific methylation site may become a new biomarker for predicting and diagnosing RA and cancer with high expression of mPGES-1. Also, our research provides new ideas and solutions for clinical diagnosis and treatment of diseases related to mPGES-1 and for targeted methylation strategy in drug development.
Journal
Biochim Biophys Acta Gene Regul Mech
Publish Year
2022
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Cancer; Inflammatory Diseases
Paper Title Cn
Paper Title En
Sinomenine increases the methylation level at specific GCG site in mPGES-1 promoter to facilitate its specific inhibitory effect on mPGES-1
Bilingual Status
semi_complete