MicroRNA-26b suppresses the metastasis of non-small cell lung cancer by targeting MIEN1 via NF-κB/MMP-9/VEGF pathways

Abstract

MicroRNAs (miRNAs) are involved in tumor initiation and progression. MiR-26b was reported to be significantly downregulated in non-small cell lung cancer (NSCLC). However, the underlying mechanisms of miR-26b involvement in the development and progression of NSCLC remains poorly understood. In the present study, we report that miR-26b suppresses cell metastasis in NSCLC through targeting migration and invasion enhancer 1 (MIEN1). We found that miR-26b was significantly downregulated and MIEN1 was significantly upregulated in both NSCLC tissues and cells lines. The expression levels of miR-26b were negatively related to those of MIEN1 mRNA in clinical NSCLC tissues. Furthermore, MIEN1 was confirmed to be a direct target of miR-26b by dual-luciferase reporter assay and MIEN1 expression was downregulated by miR-26b in NSCLC cells. In terms of function, transwell and wound healing assays demonstrated that the miR-26b remarkably inhibited invasion and migration of NSCLC cells, which was simulated by siRNA knockdown of MIEN1 and reversed by pcDNA/MIEN1 overexpression of MIEN1. Finally, we found that miR-26b could regulate NF-κB/MMP-9/VEGF pathway in NSCLC cells. In conclusion, this study revealed that miR-26b suppresses NSCLC metastasis by targeting MIEN1 via NF-κB/MMP-9/VEGF pathways, implicating a potential prognostic biomarker and therapeutic target for NSCLC treatment.