Identification and validation of a novel mature microRNA encoded by the Merkel cell polyomavirus in human Merkel cell carcinomas

Lee, S., Paulson, K. G., Murchison, E. P., Afanasiev, O. K., Alkan, C., Leonard, J. H., Byrd, D. R., Hannon, G. J., Nghiem, P. (2011) Identification and validation of a novel mature microRNA encoded by the Merkel cell polyomavirus in human Merkel cell carcinomas. Journal of Clinical Virology, 52 (3). pp. 272-275. ISSN 13866532 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/21907614
DOI: 10.1016/j.jcv.2011.08.012

Abstract

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. © 2011 Elsevier B.V.

Item Type: Paper
Uncontrolled Keywords: MCV-miR-M1 Merkel cell carcinoma Merkel cell polyomavirus MicroRNA MCV miR M1 5p unclassified drug virus RNA article cancer tissue computer model controlled study cryopreservation human human tissue in vitro study in vivo study major clinical study Merkel cell tumor Polyoma virus priority journal protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction RNA analysis RNA sequence Base Sequence Carcinoma, Merkel Cell DNA, Viral Humans MicroRNAs Polyomavirus Infections Real-Time Polymerase Chain Reaction RNA, Viral Sequence Alignment Sequence Analysis, RNA
Subjects: bioinformatics
diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
Investigative techniques and equipment
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL labs > Hannon lab
School of Biological Sciences > Publications
Depositing User: Matt Covey
Date: 2011
Date Deposited: 09 Jan 2013 16:14
Last Modified: 03 Jan 2019 21:37
PMCID: PMC3196837
Related URLs:
URI: https://repository.cshl.edu/id/eprint/26429

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