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

• Published in: Cancer science Vol. 110; no. 6; pp. 1883 - 1896
• Main Authors: Li, Xizhe, Zhu, Jiali, Liu, Yuanqi, Duan, Chaojun, Chang, Ruimin, Zhang, Chunfang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2019; John Wiley and Sons Inc
• Subjects: A549 Cells; beta Catenin - genetics; Biomarkers; Breast cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Catenin; Cell Line, Tumor; Cell Movement - genetics; Epithelial-Mesenchymal Transition - genetics; ErbB-2 protein; ErbB2; Ethics; Female; Gene Expression Regulation, Neoplastic; Humans; Immunofluorescence; Immunoprecipitation; Laboratory animals; Liver cancer; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical prognosis; Mesenchyme; Metastases; Metastasis; microRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Non-small cell lung carcinoma; non‐small‐cell lung cancer; Original; p21-Activated Kinases - genetics; Patients; Phosphorylation; Proto-Oncogene Proteins c-vav - genetics; Proto-Oncogene Proteins c-vav - metabolism; Rac1; rac1 GTP-Binding Protein - genetics; Rac1 protein; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Signal Transduction - genetics; Studies; Thoracic surgery; Tumorigenesis; VAV2; United States > US; China; microRNA; Rac1; ErbB2; VAV2; non-small-cell lung cancer
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14014

MicroRNAs have been reported to play critical roles in the regulation of non‐small‐cell cancer (NSCLC) development, but the role of microRNA (miR)‐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 quantitative RT‐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 through 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. Our results showed that microRNA (miR)‐331‐3p was significantly downregulated in non‐small‐cell cancer (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 through 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.