Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma.
EGR1
MCPyV
MCV-negative
Merkel cell carcinoma
chromatin regulator
histone
histone methyltransferase PRDM8
miRNA
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
24 Apr 2020
24 Apr 2020
Historique:
received:
23
03
2020
revised:
22
04
2020
accepted:
22
04
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
30
4
2020
Statut:
epublish
Résumé
Merkel cell carcinoma (MCC) is a deadly skin cancer, and about 80% of its cases have been shown to harbor integrated Merkel polyomavirus in the tumor cell genome. Viral oncoproteins expressed in the tumor cells are considered as the oncogenic factors of these virus-positive Merkel cell carcinoma (VP-MCC). In contrast, the molecular pathogenesis of virus-negative MCC (VN-MCC) is less well understood. Using gene expression analysis of MCC cell lines, we found histone methyltransferase PRDM8 to be elevated in VN-MCC. This finding was confirmed by immunohistochemical analysis of MCC tumors, revealing that increased PRDM8 expression in VN-MCC is also associated with increased H3K9 methylation. CRISPR-mediated silencing of PRDM8 in MCC cells further supported the histone methylating role of this protein in VN-MCC. We also identified miR-20a-5p as a negative regulator of PRDM8. Taken together, our findings provide insights into the role of PRDM8 as a histone methyltransferase in VN-MCC tumorigenesis.
Identifiants
pubmed: 32344701
pii: cancers12041057
doi: 10.3390/cancers12041057
pmc: PMC7226539
pii:
doi:
Types de publication
Journal Article
Langues
eng
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