論文 - 詳細
| RRC ID | 44791 |
|---|---|
| 著者 | Ishimoto T, Sugihara H, Watanabe M, Sawayama H, Iwatsuki M, Baba Y, Okabe H, Hidaka K, Yokoyama N, Miyake K, Yoshikawa M, Nagano O, Komohara Y, Takeya M, Saya H, Baba H. |
| タイトル | Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in cancer cells and promote redox adaptation. |
| ジャーナル | Carcinogenesis |
| Abstract |
CD44 is frequently overexpressed in a wide variety of epithelial malignancies including gastrointestinal cancer and causes resistance to currently available treatments. MicroRNAs (miRNAs) are non-coding RNAs that regulate molecular pathways in cancer by targeting various genes. The aim of this study was to investigate the regulation of CD44 expression by miRNAs and to develop new molecular targets in gastrointestinal cancer. We performed miRNA screening in six human gastrointestinal cancer cell lines and identified three candidate miRNAs that could regulate CD44 expression in gastrointestinal cancer. Among these, we focused on miR-328 and examined its functional relevance using growth assays and cytotoxicity assays. CD44 expression was reduced in gastrointestinal cancer cell lines forced to express miR-328, leading to inhibition of cancer cell growth in vitro and in vivo, and impaired resistance to chemotherapeutic drugs and reactive oxygen species (ROS). In contrast, induction of CD44 expression by miR-328 inhibitor led to promotion of cancer cell growth. Furthermore, we revealed that ROS produced by macrophages triggered CD44 expression through suppression of miR-328 in gastric cancer cells. Finally, tumor-infiltrating macrophages (CD68 and CD163) were closely related to both miR-328 downregulation and CD44 upregulation in 63 patients with surgically resected gastric cancer. These findings suggest that macrophages in the tumor microenvironment may cause increased CD44 expression through miR-328 suppression, resulting in tumor progression by enhancing ROS defense. miR-328-CD44 signaling mediated by macrophages may thus represent a potential target for the treatment of gastrointestinal cancer. |
| 巻・号 | 35(5) |
| ページ | 1003-11 |
| 公開日 | 2014-5-1 |
| DOI | 10.1093/carcin/bgt402 |
| PII | bgt402 |
| PMID | 24318997 |
| MeSH | 3' Untranslated Regions Antineoplastic Agents / pharmacology Cell Line, Tumor Cell Proliferation Drug Resistance, Neoplasm / genetics Gastrointestinal Neoplasms / genetics Gastrointestinal Neoplasms / metabolism Gene Expression Gene Expression Regulation, Neoplastic Humans Hyaluronan Receptors / genetics* Hyaluronan Receptors / metabolism Macrophages / metabolism* MicroRNAs / genetics* MicroRNAs / metabolism Neoplasms / genetics* Neoplasms / metabolism* Oxidation-Reduction Oxidative Stress / genetics Reactive Oxygen Species / metabolism* Tumor Microenvironment / genetics |
| IF | 4.603 |
| 引用数 | 57 |
| WOS 分野 | ONCOLOGY |
| 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 | Policy sources |
| 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 | Kato III(RCB2088) NUGC-4(RCB1939) HCT116(RCB2979) |