論文 - 詳細
| RRC ID | 55924 |
|---|---|
| 著者 | Kunita A, Morita S, Irisa TU, Goto A, Niki T, Takai D, Nakajima J, Fukayama M. |
| タイトル | MicroRNA-21 in cancer-associated fibroblasts supports lung adenocarcinoma progression. |
| ジャーナル | Sci Rep |
| Abstract |
Cancer-associated fibroblasts (CAFs) interact closely with cancer cells, supporting their growth and invasion. To investigate the role of microRNA-21 (miR-21) in lung adenocarcinoma, and especially in its CAF component, in situ hybridisation was applied to samples from 89 invasive lung adenocarcinoma cases. MiR-21 expression was observed in both cancer cells and CAFs. When the patients were stratified by expression, miR-21 levels in CAFs (n = 9), but not in cancer cells (n = 21), were inversely correlated with patient survival; patients with miR-21high CAFs exhibited lower survival than those with miR-21low CAFs. The underlying mechanism was investigated in vitro. Conditioned medium (CM) from A549 lung cancer cells increased miR-21 expression in MRC-5 and IMR-90 lung fibroblasts through the transforming growth factor-β pathway, and induced CAF-like morphology and migratory capacity. MiR-21 up-regulation in lung fibroblasts induced a novel CAF-secreted protein, calumenin, as well as known CAF markers (periostin, α-smooth muscle actin, and podoplanin). Moreover, CM from the lung fibroblasts increased A549 cell proliferation in a calumenin-dependent manner. Thus, miR-21 expression in lung fibroblasts may trigger fibroblast trans-differentiation into CAFs, supporting cancer progression. Therefore, CAF miR-21 represents a pivotal prognostic marker for this scar-forming cancer of the lungs. |
| 巻・号 | 8(1) |
| ページ | 8838 |
| 公開日 | 2018-6-11 |
| DOI | 10.1038/s41598-018-27128-3 |
| PII | 10.1038/s41598-018-27128-3 |
| PMID | 29892003 |
| PMC | PMC5995955 |
| MeSH | A549 Cells Adenocarcinoma of Lung / pathology* Cancer-Associated Fibroblasts / metabolism* Cell Proliferation Disease Progression Epithelial Cells / physiology Humans Lung Neoplasms / pathology* MicroRNAs / metabolism* Neoplasm Staging Survival Analysis Tokyo |
| IF | 4.011 |
| 引用数 | 15 |
| 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 | 1 |
| 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 MRC-5 |