The regulation of Neuropilin 1 expression by miR-338-3p promotes non-small cell lung cancer via changes in EGFR signaling.

Neuropilin 1 (NRP1) is a transmembrane glycoprotein that acts as a co-receptor for multiple extracellular ligands and typically performs growth-promoting functions in cancer cells. Accumulating evidence indicates that NRP1 is upregulated, and may be an independent predictor of cancer relapse and poor survival, in many cancer types, including non-small cell lung cancer (NSCLC). Recent evidence suggests that NRP1 affects tumour cell viability via the epidermal growth factor receptor (EGFR) and Erb-B2 receptor tyrosine kinase 2 (ErbB2) signalling pathways in venous endothelial cells and in multiple cancer cells. In the present study, we aimed to evaluate the role of NRP1 in NSCLC tumourigenesis and to explore a new post-transcriptional mechanism of NRP1 regulation via a microRNA that mediates EGFR signalling regulation in lung carcinogenesis. The results showed that miR-338-3p is poorly expressed and NRP1 is overexpressed in NSCLC tissues relative to their levels in adjacent noncancerous tissues. Luciferase reporter assays, quantitative real-time reverse transcription PCR, and Western blot analyses showed that NRP1 is a direct target of miR-338-3p. Overexpression of miR-338-3p in NSCLC cell lines inhibited cell proliferation in vitro and in vivo. Moreover, cell migration and invasion were inhibited by miR-338-3p overexpression. These effects occurred via the EGF signalling pathway. Our data revealed a new post-transcriptional mechanism by which miR-338-3p directly targets NRP1; this mechanism plays a role in enhancing drug sensitivity in EGFR wild-type patients with NSCLC.