Abstract
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.
Highlights
Lung cancer remains the leading cause in cancerrelated mortality in both males and females
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 non-small cell lung cancer (NSCLC) tissue samples as well as in samples from “healthy” sites, distant from the tumour region that were either positive or negative for Merkel Cell Polyoma Virus (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
The present study aimed to investigate the potential association between human polyomavirus infection and epigenetic alterations involving the expression of microRNAs in NSCLC
Summary
Lung cancer remains the leading cause in cancerrelated mortality in both males and females. 85% of lung tumors are non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma and large cell carcinoma [1]. The majority of lung cancer patients are smokers, only a minority among smokers will develop this disease, strongly suggesting that additional environmental determinants including virus infections, in a background of genetic susceptibility, drive disease initiation and progression [2]. The accumulation of genetic and epigenetic events in the respiratory epithelium is essential for lung carcinogenesis [3]. MicroRNAs (miRNAs) have been shown to be commonly dysregulated in lung cancer [4]. MicroRNAs, short, non-coding RNA molecules, are key regulators of transcription regulation and it is currently appreciated that they participate in tumorigenesis by regulating the expression of oncogenes www.impactjournals.com/oncotarget
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