RRC ID 44155
Author Tominaga E, Yuasa K, Shimazaki S, Hijikata T.
Title MicroRNA-1 targets Slug and endows lung cancer A549 cells with epithelial and anti-tumorigenic properties.
Journal Exp. Cell Res.
Abstract MicroRNA-1 (miR-1) has recently been suggested to function as a tumor suppressor. Its functional relevance was assessed by exploring structural and tumorigenic properties of lung cancer A549 cells stably transduced with retrovirus containing pre-miR-1. A549 cells overexpressing miR-1 exhibited a significant morphological change from a mesenchymal to an epithelial phenotype characterized by cell polarization and intercellular junctions. The cells showed increased expression of E-cadherin, which colocalized with cortical actin filaments and vinculin to form typical adherens junction at the apical regions of intercellular borders. Additionally, they exhibited occludin-positive tight junctions at similar apical regions. Moreover, their migratory and invasive activities were inhibited, and their sensitivity to doxorubicin was increased slightly compared to control mock-infected cells. These structural and tumorigenic properties induced by miR-1 were associated with the reduced expression of Slug, which was a transcriptional repressor of E-cadherin or an inducer of epithelial-to-mesenchymal transition. Consistently, Slug was identified as a miR-1 target by bioinformatics and a luciferase reporter assay with plasmids containing luciferase-Slug 3'UTR. Collectively, the data presented here suggest that re-expression of miR-1 may be an effective therapy that prevents cancer malignancy by converting cells from a mesenchymal phenotype to an epithelial phenotype via the downregulation of Slug.
Volume 319(3)
Pages 77-88
Published 2013-2-1
DOI 10.1016/j.yexcr.2012.10.015
PII S0014-4827(12)00444-2
PMID 23142026
MeSH Adenocarcinoma / genetics Adenocarcinoma / pathology* Base Sequence Cell Line, Tumor Cell Movement / genetics Cell Proliferation Epithelial Cells / metabolism Epithelial Cells / pathology Epithelial-Mesenchymal Transition / genetics* Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor / physiology Humans Lung Neoplasms / genetics Lung Neoplasms / pathology* MicroRNAs / genetics MicroRNAs / metabolism MicroRNAs / physiology* Neoplasm Invasiveness RNA Interference Snail Family Transcription Factors Transcription Factors / antagonists & inhibitors Transcription Factors / genetics* Transfection
IF 3.329
Times Cited 28
Human and Animal Cells