TY  - JOUR
A1  - Orouji, Elias
A1  - Peitsch, Wiebke K.
A1  - Orouji, Azadeh
A1  - Houben, Roland
A1  - Utikal, Jochen
T1  - Oncogenic role of an epigenetic reader of m\(^6\)A RNA modification: YTHDF1 in Merkel cell carcinoma
T2  - Cancers
N2  - 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 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.
KW  - Merkel cell carcinoma
KW  - Merkel cell polyomavirus
KW  - copy number variations
KW  - m\(^6\)A
KW  - RNA modification
KW  - epitranscriptome
KW  - YTHDF1
KW  - epigenetic reader
Y1  - 2020
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/20081
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-200815
SN  - 2072-6694
VL  - 12
IS  - 1
ER  -