title: MicroRNA-1 targets Slug and endows lung cancer A549 cells with epithelial and anti-tumorigenic properties.
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.
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Pharmacy, Musashino University, Nishitokyo-shi, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Tominaga
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yuasa
authors.forename: Sho
authors.initials: S
authors.lastname: Shimazaki
authors.forename: Takao
authors.initials: T
authors.lastname: Hijikata
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D014162:Transfection
chemical_list: C544547:MIRN1 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors