Oncogenic role of an epigenetic reader of m\(^6\)A RNA modification: YTHDF1 in Merkel cell carcinoma
Please always quote using this URN: urn:nbn:de:bvb:20-opus-200815
- Merkel cell carcinoma is a deadly skin cancer, which in the majority of cases is caused by the Merkel cell polyomavirus (MCPyV). The viral small T antigen is regarded as the dominant oncoprotein expressed in the tumor cells. We used genomic screening of copy number aberrations along with transcriptomic analysis to investigate regions with amplification that harbor differentially expressed genes. We identified YTHDF1, a protein that is a reader of N\(^6\)-methyladenosine (m\(^6\)A) RNA modifications, to have high copy gains and to be highlyMerkel cell carcinoma is a deadly skin cancer, which in the majority of cases is caused by the Merkel cell polyomavirus (MCPyV). The viral small T antigen is regarded as the dominant oncoprotein expressed in the tumor cells. We used genomic screening of copy number aberrations along with transcriptomic analysis to investigate regions with amplification that harbor differentially expressed genes. We identified YTHDF1, a protein that is a reader of N\(^6\)-methyladenosine (m\(^6\)A) RNA modifications, to have high copy gains and to be highly expressed in Merkel cell carcinoma. Importantly, we identified the presence of m\(^6\)A on small T antigen mRNA suggesting a relation between YTHDF1 amplification and MCPyV gene expression. Interestingly, knockdown of YTHDF1 in Merkel cell carcinoma (MCC) cell lines negatively affected the translation initiation factor eIF3 and reduced proliferation and clonogenic capacity in vitro. Furthermore, analysis of survival data revealed worse overall survival in YTHDF1\(^{high}\) MCC patients compared to YTHDF1\(^{low}\) patients. Our findings indicate a novel oncogenic role of YTHDF1 through m\(^6\)A machinery in the tumorigenesis of MCC.…
Author: | Elias Orouji, Wiebke K. Peitsch, Azadeh Orouji, Roland Houben, Jochen Utikal |
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URN: | urn:nbn:de:bvb:20-opus-200815 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie |
Language: | English |
Parent Title (English): | Cancers |
ISSN: | 2072-6694 |
Year of Completion: | 2020 |
Volume: | 12 |
Issue: | 1 |
Article Number: | 202 |
Source: | Cancers (2020) 12:1, 202. https://doi.org/10.3390/cancers12010202 |
DOI: | https://doi.org/10.3390/cancers12010202 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | Merkel cell carcinoma; Merkel cell polyomavirus; RNA modification; YTHDF1; copy number variations; epigenetic reader; epitranscriptome; m\(^6\)A |
Release Date: | 2022/05/19 |
Date of first Publication: | 2020/01/14 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |