TY  - JOUR
A1  - Orouji, Elias
A1  - Peitsch, Wiebke K.
A1  - Orouji, Azadeh
A1  - Houben, Roland
A1  - Utikal, Jochen
T1  - Unique role of histone methyltransferase PRDM8 in the tumorigenesis of virus-negative Merkel cell carcinoma
JF  - Cancers
N2  - 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.
KW  - histone
KW  - histone methyltransferase PRDM8
KW  - chromatin regulator
KW  - EGR1
KW  - miRNA
KW  - MCV-negative
KW  - Merkel cell carcinoma
KW  - MCPyV
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203815
SN  - 2072-6694
VL  - 12
IS  - 4
ER  -