Aberrant expression of miR-21, miR-376c and miR-145 and their target host genes in Merkel cell polyomavirus-positive non-small cell lung cancer
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Ismini Lasithiotaki1,2, Eliza Tsitoura2,3, Anastasios Koutsopoulos4, Eleni Lagoudaki4, Chara Koutoulaki2, George Pitsidianakis1, Demetrios A. Spandidos3, Nikolaos M. Siafakas1, George Sourvinos3,* and Katerina M. Antoniou1,2,*
1Department of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion 71110, Greece
2Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Heraklion Crete 71110, Greece
3Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion Crete 71110, Greece
4Department of Pathology, Medical School, University of Crete, Heraklion Crete 71110, Greece
*These authors have contributed equally to this work
George Sourvinos, email: [email protected]
Keywords: merkel cell polyomavirus; non-small cell lung cancer; microRNAs; signalling pathways
Received: April 23, 2016 Accepted: July 19, 2016 Published: August 11, 2016
Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a profound impact on cellular miRNA expression to control host regulatory pathways. In this study, we evaluated the expression profiles of cancer-associated and virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR-367 and miR-376c in a series of NSCLC tissue samples as well as in samples from “healthy” sites, distant from the tumour region that were either positive or negative for MCPyV DNA. miR-21 and miR-376c were significantly upregulated whereas miR-145 was significantly downregulated in the MCPyV+ve samples compared to the MCPyV-ve tumour samples. Overall, miR-21 and miR-376c expression was higher in tumour compared to healthy tissue samples. No association was observed between the miR-155, miR-146a, miR-302c and miR-367 levels and the presence of MCPyV. The expression of miR-21 target genes (Pten, Bcl-2, Daxx, Pkr, Timp3), miR-376c (Grb2, Alk7, Mmp9) and miR-145 (Oct-4, Sox2, Fascin1) and their associated pathways (Braf, Akt-1, Akt-2, Bax, Hif1a, p53) was altered between MCPyV+ve tumor samples and their corresponding controls. These results show a novel association between miR-21, miR-376c and miR-145 and their host target genes with the presence of MCPyV, suggesting a mechanism of virus-specific microRNA signature in NSCLC.
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