MiR-182-5p Promotes The Metastasis and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer By Targeting EPAS1

Abstract

BackgroundThe dysregulation of microRNAs (miRNAs) is associated with the pathogenesis of non-small cell lung cancer (NSCLC). However, the mechanism underlying miR-182-5p regulation of NSCLC progression is largely unknown. The purpose of this study was to examine the expression levels of miR-182-5p in human NSCLC and its funvtion in lung cancer cells. MethodsThe Cancer Genome Atlas (TCGA) data set was utilized to investigate the association between miR-182-5p expression and the clinicopathological characteristics and prognosis of NSCLC patients. The target genes of miR-182-5p were identified using the prediction tools PITA, miRmap, microT, miRanda, PicTar, and TargetScan. Transwell assays was used to explore the potential function of miR-182-5p in lung cancer cells. Luciferase reporter assay were performed to analyze the regulation of putative target of miR-182-5p and western blot assays were used to validate the luciferase results.ResultsmiR-182-5p was upregulated in NSCLC tissues and acted as an independent prognostic factor of tumor recurrence in NSCLC patients. Functionally, overexpression of miR-182-5p promoted lung cancer cell migration and invasion. Genome-wide gene expression analysis and luciferase report assay revealed that Endothelial PAS Domain-containing protein 1 (EPAS1) was a direct target of miR-182-5p. EPAS1 exhibited a negative correlation with miR-182-5p expression in NSCLC tissues. Univariate and multivariate survival analysis identified EPAS1 as an independent prognostic factor for overall survival and tumor recurrence in NSCLCConclusionsThese findings demonstrate that miR-182-5p functions as a tumor promoter in NSCLC progression by targeting EPAS1. It is, therefore, a potential indicator of tumor recurrence in NSCLC patients.