MicroRNA-29c functions as a tumor suppressor by targeting VEGFA in lung adenocarcinoma

作者：Lipin Liu, Nan Bi, Lihong Wu, Xiao Ding, Yu Men, Wei Zhou, Lin Li, Weimin Zhang, Susheng Shi, Yongmei Song, Lühua Wang · 发表于：Molecular Cancer · 年份：2017 · DOI：10.1186/s12943-017-0620-0 · 被引用次数：100 · 研究领域：MicroRNA in disease regulation、Circular RNAs in diseases、Kruppel-like factors research

BACKGROUND: Lung adenocarcinoma (LAD) is considered to be a highly aggressive disease with heterogeneous prognosis and the molecular mechanisms underlying tumor progression remain elusive. Growing evidence demonstrates that the dysregulation of microRNAs (miRNAs) plays an important role in various tumor processes. The aim of this study is to discover prognostic miRNA and investigate its role involved in progression of LAD. METHODS: Prognosis related miRNA was detected by miRNA microarray using formalin-fixed paraffin-embedded (FFPE) specimens from 87 patients with IIIA-N2 LAD. The cell proliferation was evaluated by Cell Titer 96 AQueous One Solution Cell Proliferation Assay (MTS), and the migration/invasion was evaluated by transwell assay. The bioinformatics methods and luciferase reporter assay were applied to detect the relationship between miRNA and its target. The mRNA and protein levels of miRNA target were determined by quantitative real time polymerase chain reaction (qRT-PCR) analysis, western blot and enzyme-linked immunosorbent assay (ELISA). Changes of angiogenesis induced by miRNA was evaluated by human umbilical vein endothelial cell (HUVEC) tube formation assay. Immunohistochemistry (IHC) analysis was performed in FFPE specimens of patients to evaluate the correlation between miR-29c with microvessel density (MVD) and vascular endothelial growth factor A (VEGFA) expression. RESULTS: MiR-29c expression downregulation was significantly associated with unfavorabl...