Biomarker: EZH2

Histology type: endometrial carcinoma

Country: Janpanese

Region: Tokyo

Study type: prospectively study

Followed up time :

Subgroup 1 name : LMS

Subgroup 1 number: 171

Subgroup 2 name: LG-ESS

Subgroup 2 number: 74

Conclusion: Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : overexpress

Expression elevation: EZH2 expression intensity was graded from 0 to 3.

Statictics: Median;Range

Cohort age: 57;20-90

Funtion description: Knockdown of EZH2 using specific siRNAs resulted in growth suppression and apoptosis induction of endometrial cancer cells, accompanied by attenuation of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased the number of cancer cell colonies.GSK126 showed additive effects with doxorubicin or cisplatin, which are conventional drugs for treatment of endometrial cancer.

Funtion Uniprot: Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599, PubMed:30923826). Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription

UniProt ID: Q15910

UniProt Link: https://www.uniprot.org/uniprotkb/Q15910/entry

Biological function from UniProt: Biological rhythms, Transcription, Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: In the ovary, expressed in primordial follicles and oocytes and also in external follicle cells (at protein level) (PubMed:31451685). Expressed in many tissues (PubMed:14532106). Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis (PubMed:14532106).

Subcellular UniProt: #Nucleus

Alternative name from UniProt:

Caution: Two variants of the PRC2 complex have been described, termed PRC3 and PRC4. Each of the three complexes may include a different complement of EED isoforms, although the precise sequences of the isoforms in each complex have not been determined. The PRC2 and PRC4 complexes may also methylate 'Lys-26' of histone H1 in addition to 'Lys-27' of histone H3 (PubMed:15099518 and PubMed:15684044), although other studies have demonstrated no methylation of 'Lys-26' of histone H1 by PRC2 (PubMed:16431907).

Catalytic activity: L-lysyl27-[histone H3] + 3 S-adenosyl-L-methionine = 3 H+ + N6,N6,N6-trimethyl-L-lysyl27-[histone H3] + 3 S-adenosyl-L-homocysteine

Recommended name: Histone-lysine N-methyltransferase EZH2

Gene name from HGNC: EZH2 (ENX-1, EZH1, KMT6, KMT6A)

HPA class: Cancer-related genes Disease related genes Enzymes FDA approved drug targets Human disease related genes Metabolic proteins Plasma proteins

AlphaFold DB: Q15910

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q15910

Induction: Expression is induced by E2F1, E2F2 and E2F3. Expression is reduced in cells subject to numerous types of stress including UV-, IR- and bleomycin-induced DNA damage and by activation of p53/TP53.

Developmental stage: Expression decreases during senescence of embryonic fibroblasts (HEFs). Expression peaks at the G1/S phase boundary.

HPA link: https://www.proteinatlas.org/ENSG00000106462-EZH2

Tissue specificity RNA from HPA: Tissue enhanced (bone marrow, lymphoid tissue, testis)

Tissue expression from HPA: Nuclear expression in several tissues, most abundant in testis and lymphoid tissues.

Single cell type specificity Cell type enhanced (Spermatocytes, Early spermatids)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Nucleoplasm (Single cell variability)

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable), liver cancer (unfavorable), melanoma (unfavorable) and stomach cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000106462-EZH2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000106462-EZH2/pathology/endometrial+cancer

Expression figure legend: Immunohistochemical staining of EZH2 in a tissue microarray

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522273/figure/F3/

Survival figure legend: PFS (E) and OS (F) were analyzed by the Kaplan-Meier method and log-rank test.

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522273/figure/F3/

Phenotype ID: 277590

Disease: Weaver syndrome (WVS)

Note1: The disease is caused by variants affecting the gene represented in this entry

OMIM: 601573

OMIM link1: https://www.omim.org/entry/277590

OMIM link2: https://www.omim.org/entry/601573

HGNC ID: HGNC:3527

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3527