title: Overexpression of MicroRNA-27b Inhibits Proliferation, Migration, and Invasion via Suppression of MET Expression.
abstract: MicroRNA-27b (miR-27b) was recently found to be significantly downregulated in different human cancers. However, evidence of the function of miR-27b in non-small cell lung cancer (NSCLC) remains limited. In this study, we aimed to investigate novel miR-27b-mediated targets or signaling pathways associated with the tumorigenesis and metastasis of NSCLC. Real-time (RT) PCR was performed to examine miR-27b expression in NSCLC specimens. MTT assay, wound-healing assay, and Transwell assay were used to determine cell proliferation, migration, and invasion. Our data indicated that the miR-27b levels were significantly decreased in NSCLC specimens and cell lines (SK-MES-1, H358, H460, A549, and H1229) when compared to matched normal adjacent tissues and normal human lung epithelial cell lines, respectively. Restoration of miR-27b significantly inhibited the proliferation, migration, and invasion of A549 cells. We then conducted in silico analysis and luciferase reporter gene assay and identified MET, a receptor tyrosine kinase, as a direct target of miR-27b in NSCLC cells. Moreover, overexpression of MET rescued the suppressive effect of miR-27b on the proliferation, migration, and invasion of A549 cells, suggesting that MET acts as a downstream effecter of miR-27b in NSCLC cells. In summary, our study identified a novel miR-27b/MET signaling pathway involved in the cell proliferation, migration, and invasion of NSCLC, and identification of miR-27b-mediated novel signaling pathways may help reveal the molecular mechanism underlying the development and malignant progression of this disease.
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South UniversityChangsha, HunanP.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityChangsha, HunanP.R. China.
authors.forename: Yanglin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Central South UniversityChangsha, HunanP.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South UniversityChangsha, HunanP.R. China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South UniversityChangsha, HunanP.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D019859:Proto-Oncogene Proteins c-met