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

Abstract

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.

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

“…Previously, it was demonstrated NRP1 expression in NSCLC tissues and cells was higher than that in adjacent non-cancerous lung tissues and bronchial epithelial cells (22). In this study, to elucidate the role of NRP1 in NSCLC metastasis, NRP1 was stably knocked down in A549 (adenocarcinoma) and H226 (squamous carcinoma) cells.…”

“…A previous study by the authors demonstrated that the expression of NRP1 was high in NSCLC tissues and was associated with a poorer survival of patients (22). In addition, NRP1 can promote NSCLC cell proliferation and migration via the EGFR signaling pathway (22). Taken together, it was thus hypothesized that dysregulated NRP1 can influence TGF-β1-induced EMT.…”

“…NRP1 is a transmembrane glycoprotein that binds to various extracellular ligands, including class III/IV semaphorins (19), certain isoforms of vascular endothelial growth factor (VEGF) (20), TGF-β1 (15), and platelet-derived growth factor (PDGF) (21). A previous study by the authors demonstrated that the expression of NRP1 was high in NSCLC tissues and was associated with a poorer survival of patients (22). In addition, NRP1 can promote NSCLC cell proliferation and migration via the EGFR signaling pathway (22).…”

miR‑519 regulates the proliferation of breast cancer cells via targeting human antigen�R

“…MicroRNAs (miRs) represent a class of 21-23 nucleotides long small non-coding RNAs that can act as oncogenes (8) or tumor suppressors (9) in various types of cancer, including gastrointestinal (10), liver (11), pancreatic (12), ovarian (13), lung (14) and breast cancer (15). miRs can bind directly to the 3'-untranslated region (UTR) of target genes to negatively regulate protein expression (16).…”

Neuropilin 1 modulates TGF-β1-induced epithelial–mesenchymal transition in non-small cell lung cancer

“…Our previous study showed that NRP1 is up-regulated in NSCLC tissues and associated with poorer survival in patients. Meanwhile NRP1 can promote NSCLC cells proliferation and migration via EGFR signaling pathway [22]. Taken together, we hypothesized that dysregualted NRP1 can influence TGF-β1-induced EMT.…”