The regulation of Neuropilin 1 expression by miR‐338‐3p promotes non‐small cell lung cancer via changes in EGFR signaling. Issue 6 (27th February 2019)

• Record Type: Journal Article
• Authors: Ding, Zongli; Zhu, Jianjie; Zeng, Yuanyuan; Du, Wenwen; Zhang, Yang; Tang, Haicheng; Zheng, Yulong; Qin, Hualong; Liu, Zeyi; Huang, Jian‐an
• Is Part Of: Molecular carcinogenesis. Volume 58:Issue 6(2019)
• Page Start: 1019
• Page End: 1032
• Publication Date: 2019-02-27
• Subjects: epidermal growth factor receptor -- EGFR -- miR‐338‐3p -- Neuropilin 1 -- non‐small cell lung cancer -- NSCLC; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22990
• Languages: English
• ISSNs: 0899-1987

Abstract

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.