Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma
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...
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MDPI AG
2020-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/4/1057 |
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| author | Elias Orouji Wiebke K. Peitsch Azadeh Orouji Roland Houben Jochen Utikal |
| author_facet | Elias Orouji Wiebke K. Peitsch Azadeh Orouji Roland Houben Jochen Utikal |
| author_sort | Elias Orouji |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T20:14:43Z |
| format | Article |
| id | doaj.art-af5986ddceb341439a6e83e59d266fa5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:14:43Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-af5986ddceb341439a6e83e59d266fa52023-11-19T22:38:30ZengMDPI AGCancers2072-66942020-04-01124105710.3390/cancers12041057Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell CarcinomaElias Orouji0Wiebke K. Peitsch1Azadeh Orouji2Roland Houben3Jochen Utikal4Skin Cancer Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDepartment of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, GermanyDepartment of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Würzburg, 97080 Würzburg, GermanySkin Cancer Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyMerkel 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.https://www.mdpi.com/2072-6694/12/4/1057histonehistone methyltransferase PRDM8chromatin regulatorEGR1miRNAMCV-negative |
| spellingShingle | Elias Orouji Wiebke K. Peitsch Azadeh Orouji Roland Houben Jochen Utikal Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma Cancers histone histone methyltransferase PRDM8 chromatin regulator EGR1 miRNA MCV-negative |
| title | Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma |
| title_full | Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma |
| title_fullStr | Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma |
| title_full_unstemmed | Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma |
| title_short | Unique Role of Histone Methyltransferase PRDM8 in the Tumorigenesis of Virus-Negative Merkel Cell Carcinoma |
| title_sort | unique role of histone methyltransferase prdm8 in the tumorigenesis of virus negative merkel cell carcinoma |
| topic | histone histone methyltransferase PRDM8 chromatin regulator EGR1 miRNA MCV-negative |
| url | https://www.mdpi.com/2072-6694/12/4/1057 |
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