Tumor-targeting TRAIL expression mediated by miRNA response elements suppressed growth of uveal melanoma cells

doi:10.1016/j.molonc.2013.08.003

IOCAS-IR > 实验海洋生物学重点实验室

	Tumor-targeting TRAIL expression mediated by miRNA response elements suppressed growth of uveal melanoma cells
	Liu, Jia 2; Ma, Leina 3; Li, Caixin 1; Zhang, Ziyu 1; Yang, Guanghua 1,4; Zhang, Wenwei 1,5; Yang, GH
	2013-12-01
发表期刊	MOLECULAR ONCOLOGY
ISSN	1574-7891
卷号	7 期号:6 页码:1043-1055
文章类型	Article
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.; 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.
关键词	Uveal Melanoma Adenovirus Mirna Trail
学科领域	Oncology
DOI	10.1016/j.molonc.2013.08.003
URL	查看原文
收录类别	SCI
语种	英语
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000328176400005
WOS关键词	APOPTOSIS-INDUCING LIGAND ; CANCER-CELLS ; ONCOLYTIC ADENOVIRUS ; GENE-TRANSFER ; HUMAN HEPATOCYTES ; LIVER METASTASIS ; DEATH ; PROLIFERATION ; RECEPTORS ; SUSCEPTIBILITY
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
引用统计	被引频次：44[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/16670
专题	实验海洋生物学重点实验室
通讯作者	Yang, GH
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
第一作者单位	中国科学院海洋研究所
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.,...&Yang, GH.(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.

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