Abstract
BACKGROUND: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including non-small cell lung cancer (NSCLC). Here, we investigated anomalous miR-613 expression and its possible functional consequences in primary NSCLC samples and NSCLC-derived cell lines. METHODS: The expression of miR-613 was measured by quantitative RT-PCR in 56 primary NSCLC tissues and adjacent non-tumor tissues. The effect of miR-613 up- or down-regulation in NSCLC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. RESULTS: Using quantitative RT-PCR, we found that miR-613 was down-regulated in 76.8 % (43/56) of the primary NSCLC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-613 mimic used reduced in vitro cell viability and colony formation by inducing cell cycle arrest in NSCLC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-613 inhibitor used increased the viability and colony forming capacity of NSCLC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-613 using in silico Miranda predictions. Subsequent dual-luciferase reporter assays revealed that CDK4 acts as a direct target of miR-613. Concordantly, we found that both miR-613 mimics and inhibitors could decrease and increase CDK4 protein levels in NSCLC-derived cells, respectively. CONCLUSIONS: From our results we conclude that miR-613 may act as a tumor suppressor in NSCLC and may serve as a tool for miRNA-based NSCLC therapy.