Molecule Information

General Information of the Molecule (ID: Mol04210)

Name	Histone H3 lysine 27 trimethylation (H3K27me3) ,Homo sapiens
Synonyms	Histone H3 lysine 27 trimethylation (H3K27me3) Click to Show/Hide
Molecule Type	Protein
*Click to Show/Hide the Complete Species Lineage*
Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

Investigative Drug(s)

1 drug(s) in total

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3-Deazaneplanocin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Disease Class: cancer [ICD-11: 2D4Z]				[1]
Sensitive Disease	cancer [ICD-11: 2D4Z]			Disease Info
Sensitive Drug	3-Deazaneplanocin			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	B16 cells	Skin	Homo sapiens (Human)	CVCL_F936
Experiment for Molecule Alteration	Western blot assay
Experiment for Drug Resistance	WST-8 assay
Mechanism Description	The?protein expression?of the?enhancer of zeste homolog 2?(EZH2),?histone methyltransferase?and its target?histone H3?trimethylation at lysine 27 (H3K27Me3) level increased under hypoxia. The induction of H3K27Me3 under hypoxia was suppressed by EZH2?siRNA?and 3-deazaneplanocin A (DZNep), an EZH2 inhibitor. Furthermore, both EZH2?siRNA?and DZNep significantly reduced the?cell viability?after SN-38 treatment and improved the chemoresistance to SN-38 under hypoxia. These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a?histone methyltransferase?EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of?histone methylation?induced under hypoxic?tumor microenvironment.

References

Ref 1	3-deazaneplanocin A, a histone methyltransferase inhibitor, improved the chemoresistance induced under hypoxia in melanoma cells. Biochem Biophys Res Commun. 2023 Oct 15;677:26-30.