論文 - 詳細
| RRC ID | 68848 |
|---|---|
| 著者 | Kitamura K, Seike M, Okano T, Matsuda K, Miyanaga A, Mizutani H, Noro R, Minegishi Y, Kubota K, Gemma A. |
| タイトル | MiR-134/487b/655 cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. |
| ジャーナル | Mol Cancer Ther |
| Abstract |
Epithelial-mesenchymal transition (EMT) has recently been recognized as a key element of cell invasion, migration, metastasis, and drug resistance in several types of cancer, including non-small cell lung cancer (NSCLC). Our aim was to clarify microRNA (miRNA)-related mechanisms underlying EMT followed by acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in NSCLC. miRNA expression profiles were examined before and after transforming growth factor β1 (TGF-β1) exposure in four human adenocarcinoma cell lines with or without EMT. Correlation between expressions of EMT-related miRNAs and resistance to EGFR-TKI gefitinib was evaluated. miRNA array and real-time quantitative reverse transcription PCR (qRT-PCR) revealed that TGF-β1 significantly induced overexpression of miR-134, miR-487b, and miR-655, which belong to the same cluster located on chromosome 14q32, in lung adenocarcinoma cells with EMT. MAGI2 (membrane-associated guanylate kinase, WW, and PDZ domain-containing protein 2), a predicted target of these miRNAs and a scaffold protein required for PTEN, was diminished in A549 cells with EMT after the TGF-β1 stimulation. Overexpression of miR-134 and miR-487b promoted the EMT phenomenon and affected the drug resistance to gefitinib, whereas knockdown of these miRNAs inhibited the EMT process and reversed TGF-β1-induced resistance to gefitinib. Our study demonstrated that the miR-134/487b/655 cluster contributed to the TGF-β1-induced EMT phenomenon and affected the resistance to gefitinib by directly targeting MAGI2, in which suppression subsequently caused loss of PTEN stability in lung cancer cells. The miR-134/miR-487b/miR-655 cluster may be a new therapeutic target in patients with advanced lung adenocarcinoma, depending on the EMT phenomenon. |
| 巻・号 | 13(2) |
| ページ | 444-53 |
| 公開日 | 2014-2-1 |
| DOI | 10.1158/1535-7163.MCT-13-0448 |
| PII | 1535-7163.MCT-13-0448 |
| PMID | 24258346 |
| MeSH | Adaptor Proteins, Signal Transducing Adenocarcinoma / genetics Adenocarcinoma / metabolism Adenocarcinoma / pathology Blotting, Western Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / metabolism Carcinoma, Non-Small-Cell Lung / pathology Carrier Proteins / genetics* Carrier Proteins / metabolism Cell Line, Tumor Drug Resistance, Neoplasm / genetics Epithelial-Mesenchymal Transition / drug effects* Epithelial-Mesenchymal Transition / genetics ErbB Receptors / antagonists & inhibitors ErbB Receptors / metabolism Gefitinib Gene Expression Profiling Gene Expression Regulation, Neoplastic Guanylate Kinases Humans Lung Neoplasms / genetics Lung Neoplasms / metabolism Lung Neoplasms / pathology Membrane Proteins / metabolism MicroRNAs / genetics* Oligonucleotide Array Sequence Analysis PTEN Phosphohydrolase / metabolism Protein Kinase Inhibitors / pharmacology Quinazolines / pharmacology Reverse Transcriptase Polymerase Chain Reaction Transforming Growth Factor beta1 / pharmacology* |
| IF | 5.615 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) LC-2/ad(RCB0440) RERF-LC-KJ(RCB1313) |