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Selective expression of tumor necrosis factor-related apoptosis-inducing ligand mediated by microRNA suppresses renal carcinoma growth

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Abstract

Renal cell carcinoma (RCC) is the most common types among kidney cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) strongly induces apoptosis in RCC. However, TRAIL therapy also leads to hepatotoxicity. To improve the biosafety, we inserted miRNA response elements (MREs) of miR-138, miR-199, and miR-122 into an adenoviral vector, Ad-TRAIL-3MREs, to restrict TRAIL expression within RCC cells. Luciferase assays showed that MREs can regulate the expression of exogenous gene in RCC cells. Ad-TRAIL-3MREs selectively expressed TRAIL and induce apoptosis in RCC cells, but not in normal cells. MTT assays revealed that Ad-TRAIL-3MREs reduced viability of RCC cells without cytotoxicity to normal cells. Ad-TRAIL-3MREs suppressed the growth of ACHN tumors and exerted no hepatotoxicity in vivo. Collectively, we generated a TRAIL-expressing adenoviral vector under the regulation of MREs. This miRNA-based gene therapy may be a promising strategy for RCC treatment.

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Authors and Affiliations

  1. Department of Urology, China Japan Union Hospital of Jilin University, Changchun, 130033, China

    Zhuo Zhang, Haiyan Zhang, Hongyan Li, Xiaoliang Chen, Meihan Liu, Dayu Liu, Yuanyuan Zhao & Xiangbo Kong

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  1. Zhuo Zhang
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  2. Haiyan Zhang
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  3. Hongyan Li
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  4. Xiaoliang Chen
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  5. Meihan Liu
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  8. Xiangbo Kong
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Correspondence to Xiangbo Kong.

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11010_2014_2025_MOESM1_ESM.ppt

Supplementary Figure Ad-TRAIL-3MREs depleted endogenous miR-138, miR-199 and miR-122 in normal cells. a The levels of miR-138, miR-199 and miR-122 were examined by qPCR assays in HK-2 and L-02 cells infected with Ad-TRAIL or Ad-TRAIL-3MREs (10 MOI) for 48 h. The bars represented Mean ± SD. b EZH2, GRP78 and MEF2D mRNA were also assessed in normal cell lines 48 h after the treatment of Ad-TRAIL or Ad-TRAIL-3MREs (10 MOI). Mean ± SD were shown. (PPT 133 kb)

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Zhang, Z., Zhang, H., Li, H. et al. Selective expression of tumor necrosis factor-related apoptosis-inducing ligand mediated by microRNA suppresses renal carcinoma growth. Mol Cell Biochem 392, 125–134 (2014). https://doi.org/10.1007/s11010-014-2025-3

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  • DOI: https://doi.org/10.1007/s11010-014-2025-3

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