MicroRNA‐331‐3p inhibits epithelial‐mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β‐catenin axis in non‐small‐cell lung cancer

Abstract

MicroRNAs have been demonstrated to have critical roles in the regulation of NSCLC development, but the role of microRNA‐331‐3p in NSCLC is still unclear. In this study, the expression levels of miR‐331‐3p in NSCLC tumor tissues and adjacent normal tissues were examined by qRT‐PCR, and the relationship between miR‐331‐3p expression and patient clinicopathological characteristics was analyzed. The effects of miR‐331‐3p on epithelial‐mesenchymal transition (EMT), migration and metastasis of NSCLC cells were determined in vitro and vivo. Direct functional targets of miR‐331‐3p were identified by luciferase reporter assay, Western blot assay, immunohistochemical staining, and rescue assay. The downstream pathway regulated by miR‐331‐3p was identified by immunofluorescence, immunoprecipitation and Rac1 activity examination. Our results showed that miR‐331‐3p was significantly downregulated in NSCLC tumor tissues and was correlated with clinicopathological characteristics, and miR‐331‐3p could be an independent prognostic marker for NSCLC patients. Furthermore, miR‐331‐3p significantly suppressed EMT migration and metastasis of NSCLC cells in vitro and in vivo. Both ErbB2 and VAV2 were direct functional targets of miR‐331‐3p. The activities of Rac1, PAK1, and β‐catenin were regulated by miR‐331‐3p via ErbB2 and VAV2 targeting. These results indicated that miR‐331‐3p suppresses EMT, migratory capacity, and metastatic ability by targeting ErbB2 and VAV2 through the Rac1/PAK1/β‐Catenin axis in NSCLC.