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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2013

Open Access 01-12-2013 | Research

microRNA response elements-regulated TRAIL expression shows specific survival-suppressing activity on bladder cancer

Authors: Youguang Zhao, Ying Li, Liang Wang, Hang Yang, Qingtang Wang, Haiyan Qi, Shadan Li, Peng Zhou, Ping Liang, Qiwu Wang, Xiaowei Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2013

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Abstract

Background

Bladder transitional cell carcinoma greatly threatens human health all over the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows a strong apoptosis-inducing effect on a variety of cancer cells including bladder cancer. However, adenovirus-mediated TRAIL expression still showed cytotoxicity to normal cells mainly due to lack of tumor specificity.

Methods

To solve the problem, we applied miRNA response elements (MREs) of miR-1, miR-133 and miR-218 to confer TRAIL expression with specificity to bladder cancer cells.

Results

Expression of miR-1, miR-133 and miR-218 was greatly decreased in bladder cancer than normal bladder tissue. Luciferase assay showed that application of the 3 MREs was able to restrain exogenous gene expression to within bladder cancer cells. Subsequently, we constructed a recombinant adenovirus with TRAIL expression regulated by MREs of miR-1, miR-133 and miR-218, namely Ad-TRAIL-MRE-1-133-218. qPCR, immunoblotting and ELISA assays demonstrated that Ad-TRAIL-MRE-1-133-218 expressed in bladder cancer cells, rather than normal bladder cells. The differential TRAIL expression also led to selective apoptosis-inducing and growth-inhibiting effect of Ad-TRAIL-MRE-1-133-218 on bladder cancers. Finally, bladder cancer xenograft in mouse models further confirmed that Ad-TRAIL-MRE-1-133-218 effectively suppressed the growth of bladder cancers.

Conclusions

Collectively, we demonstrated that MREs-based TRAIL delivery into bladder cancer cells was feasible and efficient for cancer gene therapy.
Appendix
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Metadata
Title
microRNA response elements-regulated TRAIL expression shows specific survival-suppressing activity on bladder cancer
Authors
Youguang Zhao
Ying Li
Liang Wang
Hang Yang
Qingtang Wang
Haiyan Qi
Shadan Li
Peng Zhou
Ping Liang
Qiwu Wang
Xiaowei Li
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2013
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-32-10

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