Tumor-targeting TRAIL expression mediated by miRNA response elements suppressed growth of uveal melanoma cells
文献类型：期刊论文
| 作者 | Liu, Jia2; Ma, Leina3; Li, Caixin1; Zhang, Ziyu1; Yang, Guanghua1,4; Zhang, Wenwei1,5 |
| 刊名 | MOLECULAR ONCOLOGY
 |
| 出版日期 | 2013-12-01 |
| 卷号 | 7期号:6页码:1043-1055 |
| ISSN号 | 1574-7891 |
| 关键词 | Uveal melanoma Adenovirus miRNA TRAIL |
| 通讯作者 | Yang, GH |
| 中文摘要 | Malignant uveal melanoma severely damages eye function and is prone to metastasize to other organs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent to treat uveal melanoma because of its induction of apoptosis in cancer cells both at primary and metastatic sites. However, TRAIL therapy lacks tumor specificity in the current delivery systems for uveal melanoma treatment, thereby causing cytotoxiciy to normal tissues. To improve uveal melanoma specificity of adenovirus-based TRAIL introduction, we used miRNA response elements (MREs) of miR-34a, miR-137 and miR-182, which have been shown to have reduced expression in uveal melanoma cells, to regulate its expression. miR-34a, miR-137 and miR-182 all had lower expression levels in uveal melanoma cell lines, compared with normal cells. MREs-regulated luciferase activity was reduced in normal cell lines, but not significantly attenuated in uveal melanoma cells. The infection of MRE-regulated TRAIL-expressing adenoviral vector (Ad-TRAIL-3MREs) led to high level of TRAIL expression in uveal melanoma cell lines, but not in normal cells. Strong expression of TRAIL had a high anti-tumor capacity by inducing apoptosis in uveal melanoma cells. In contrast, Ad-TRAIL-3MREs had no cytotoxicity to normal cell lines. Animal experiments further confirmed tumor-suppressing effect of Ad-TRAIL-3MREs on uveal melanoma xenografts and its biosafety to hepatic tissues. Collectively, we constructed an MRE-directed TRAIL-expressing adenoviral vector and provided evidence that this vector possessed high anti-tumor activity and uveal melanoma specificity. Crown Copyright (C) 2013 Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. |
| 英文摘要 | Malignant uveal melanoma severely damages eye function and is prone to metastasize to other organs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent to treat uveal melanoma because of its induction of apoptosis in cancer cells both at primary and metastatic sites. However, TRAIL therapy lacks tumor specificity in the current delivery systems for uveal melanoma treatment, thereby causing cytotoxiciy to normal tissues. To improve uveal melanoma specificity of adenovirus-based TRAIL introduction, we used miRNA response elements (MREs) of miR-34a, miR-137 and miR-182, which have been shown to have reduced expression in uveal melanoma cells, to regulate its expression. miR-34a, miR-137 and miR-182 all had lower expression levels in uveal melanoma cell lines, compared with normal cells. MREs-regulated luciferase activity was reduced in normal cell lines, but not significantly attenuated in uveal melanoma cells. The infection of MRE-regulated TRAIL-expressing adenoviral vector (Ad-TRAIL-3MREs) led to high level of TRAIL expression in uveal melanoma cell lines, but not in normal cells. Strong expression of TRAIL had a high anti-tumor capacity by inducing apoptosis in uveal melanoma cells. In contrast, Ad-TRAIL-3MREs had no cytotoxicity to normal cell lines. Animal experiments further confirmed tumor-suppressing effect of Ad-TRAIL-3MREs on uveal melanoma xenografts and its biosafety to hepatic tissues. Collectively, we constructed an MRE-directed TRAIL-expressing adenoviral vector and provided evidence that this vector possessed high anti-tumor activity and uveal melanoma specificity. Crown Copyright (C) 2013 Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. |
| 学科主题 | Oncology |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Oncology |
| 研究领域[WOS] | Oncology |
| 关键词[WOS] | APOPTOSIS-INDUCING LIGAND ; CANCER-CELLS ; ONCOLYTIC ADENOVIRUS ; GENE-TRANSFER ; HUMAN HEPATOCYTES ; LIVER METASTASIS ; DEATH ; PROLIFERATION ; RECEPTORS ; SUSCEPTIBILITY |
| 收录类别 | SCI |
| 原文出处 | 10.1016/j.molonc.2013.08.003 |
| 语种 | 英语 |
| WOS记录号 | WOS:000328176400005 |
| 公开日期 | 2014-07-17 |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/16670]  |
| 专题 | 海洋研究所_实验海洋生物学重点实验室 |
| 作者单位 | 1.Telebio Biomed Co Ltd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China 3.Ocean Univ China, Sch Med & Pharm, Dept Mol Biol, Qingdao 266003, Peoples R China 4.Tongji Univ, East Hosp, Res Ctr Translat Med, Sch Med, Shanghai 200120, Peoples R China 5.Hop Kremlin Bicetre, INSERM U972, F-94276 Le Kremlin Bicetre, France |
| 推荐引用方式 GB/T 7714 | Liu, Jia,Ma, Leina,Li, Caixin,et al. Tumor-targeting TRAIL expression mediated by miRNA response elements suppressed growth of uveal melanoma cells[J]. MOLECULAR ONCOLOGY,2013,7(6):1043-1055. |
| APA | Liu, Jia,Ma, Leina,Li, Caixin,Zhang, Ziyu,Yang, Guanghua,&Zhang, Wenwei.(2013).Tumor-targeting TRAIL expression mediated by miRNA response elements suppressed growth of uveal melanoma cells.MOLECULAR ONCOLOGY,7(6),1043-1055. |
| MLA | Liu, Jia,et al."Tumor-targeting TRAIL expression mediated by miRNA response elements suppressed growth of uveal melanoma cells".MOLECULAR ONCOLOGY 7.6(2013):1043-1055. |
入库方式： OAI收割
来源：海洋研究所
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