| RRC ID |
44155
|
| 著者 |
Tominaga E, Yuasa K, Shimazaki S, Hijikata T.
|
| タイトル |
MicroRNA-1 targets Slug and endows lung cancer A549 cells with epithelial and anti-tumorigenic properties.
|
| ジャーナル |
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.
|
| 巻・号 |
319(3)
|
| ページ |
77-88
|
| 公開日 |
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 |
3.383
|
| 引用数 |
28
|
|
WOS 分野
|
ONCOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
A549(RCB0098)
PC-9(RCB0446)
RERF-LC-KJ(RCB1313)
LC-2/ad(RCB0440) |
