BACKGROUND: Merkel cell polyomavirus (MCPyV) is present in approximately 80% of human Merkel cell carcinomas (MCCs). A previous in silico prediction suggested MCPyV encodes a microRNA (miRNA) that may regulate cellular and viral genes. OBJECTIVES: To determine the presence and prevalence of a putative MCPyV-encoded miRNA in human MCC tumors. STUDY DESIGN: Over 30 million small RNAs from 7 cryopreserved MCC tumors and 1 perilesional sample were sequenced. 45 additional MCC tumors were examined for expression of an MCPyV-encoded mature miRNA by reverse transcription real-time PCR. RESULTS: An MCPyV-encoded mature miRNA, "MCV-miR-M1-5p", was detected by direct sequencing in 2 of 3 MCPyV-positive MCC tumors. Although a precursor miRNA, MCV-miR-M1, had been predicted in silico and studied in vitro by Seo et al., no MCPyV-encoded miRNAs have been directly detected in human tissues. Importantly, the mature sequence of MCV-miR-M1 found in vivo was identical in all 79 reads obtained but differed from the in silico predicted mature miRNA by a 2-nucleotide shift, resulting in a distinct seed region and a different set of predicted target genes. This mature miRNA was detected by real-time PCR in 50% of MCPyV-positive MCCs (n = 38) and in 0% of MCPyV-negative MCCs (n = 13). CONCLUSIONS: MCV-miR-M1-5p is expressed at low levels in 50% of MCPyV-positive MCCs. This virus-encoded miRNA is predicted to target genes that may play a role in promoting immune evasion and regulating viral DNA replication.
BACKGROUND:Merkel cell polyomavirus (MCPyV) is present in approximately 80% of humanMerkel cell carcinomas (MCCs). A previous in silico prediction suggested MCPyV encodes a microRNA (miRNA) that may regulate cellular and viral genes. OBJECTIVES: To determine the presence and prevalence of a putative MCPyV-encoded miRNA in human MCC tumors. STUDY DESIGN: Over 30 million small RNAs from 7 cryopreserved MCC tumors and 1 perilesional sample were sequenced. 45 additional MCC tumors were examined for expression of an MCPyV-encoded mature miRNA by reverse transcription real-time PCR. RESULTS: An MCPyV-encoded mature miRNA, "MCV-miR-M1-5p", was detected by direct sequencing in 2 of 3 MCPyV-positive MCC tumors. Although a precursor miRNA, MCV-miR-M1, had been predicted in silico and studied in vitro by Seo et al., no MCPyV-encoded miRNAs have been directly detected in human tissues. Importantly, the mature sequence of MCV-miR-M1 found in vivo was identical in all 79 reads obtained but differed from the in silico predicted mature miRNA by a 2-nucleotide shift, resulting in a distinct seed region and a different set of predicted target genes. This mature miRNA was detected by real-time PCR in 50% of MCPyV-positive MCCs (n = 38) and in 0% of MCPyV-negative MCCs (n = 13). CONCLUSIONS: MCV-miR-M1-5p is expressed at low levels in 50% of MCPyV-positive MCCs. This virus-encoded miRNA is predicted to target genes that may play a role in promoting immune evasion and regulating viral DNA replication.
Authors: Roland Houben; Masahiro Shuda; Rita Weinkam; David Schrama; Huichen Feng; Yuan Chang; Patrick S Moore; Jürgen C Becker Journal: J Virol Date: 2010-05-05 Impact factor: 5.103
Authors: M Groettrup; A Soza; M Eggers; L Kuehn; T P Dick; H Schild; H G Rammensee; U H Koszinowski; P M Kloetzel Journal: Nature Date: 1996-05-09 Impact factor: 49.962
Authors: Gian Maria Fimia; Anastassia Stoykova; Alessandra Romagnoli; Luigi Giunta; Sabrina Di Bartolomeo; Roberta Nardacci; Marco Corazzari; Claudia Fuoco; Ahmet Ucar; Peter Schwartz; Peter Gruss; Mauro Piacentini; Kamal Chowdhury; Francesco Cecconi Journal: Nature Date: 2007-06-24 Impact factor: 49.962