Abstract
Lung cancer, formerly known to be solely a smoker's disease, may now be considered the outcome of environmental and genetic interactions, including viral infections. Merkel Cell Polyoma Virus (MCPyV) has already been associated with human lung cancer. Although the molecular pathways are yet to be elucidated, microRNA epigenetic aberrations could cause altered regulation of gene expression.
The current study intended to investigate the expression profile of microRNAs (miR-21, miR-367, miR-155,miR-146a, miR-302c, miR-376c and miR-145) in paraffin embedded tissue samples in a primary non-small cell lung cancer (NSCLC) patients cohort.
The presence of MCPyV DNA, microRNA expression profiles and target genes' expression profiles were determined via Real-Time PCR.
MiR-21 and miR-376c were significantly upregulated in all McPyV positive tumor samples compared to controls, while their target genes (Bcl-2, PTEN, EIF4A2, TIMP3, AKT, Myc, RB1, BRAF, RKIP andALK7, MMP9 respectively) showed significant dysregulation in all McPyV positive NSCLC samples compared to controls, with significant microRNA-target gene correlation.
These results implicate for the first time miR-21 and miR-376c with MCPyV and human NSCLC.
MiR-21 –already linked to poor NSCLC survival- targets various cell cycle genes, including Bcl-2, previously implicated in the MCPyV-NSCLC interaction. Events originating from the deregulation of miR-21 and miR-376c and their targets in MCPyV-positive NSCLC samples could be cardinal in tumorigenesis, however their role is yet to be elucidated.
- Copyright ©ERS 2015