2013年2月
MicroRNA-1 targets Slug and endows lung cancer A549 cells with epithelial and anti-tumorigenic properties
EXPERIMENTAL CELL RESEARCH
- ,
- ,
- ,
- 巻
- 319
- 号
- 3
- 開始ページ
- 77
- 終了ページ
- 88
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.yexcr.2012.10.015
- 出版者・発行元
- ELSEVIER INC
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 over-expressing 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. (c) 2012 Elsevier Inc. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.yexcr.2012.10.015
- ISSN : 0014-4827
- PubMed ID : 23142026
- Web of Science ID : WOS:000314145200008