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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12

AUTHORS

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

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. More... »

PAGES

10

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1756-9966-32-10

    DOI

    http://dx.doi.org/10.1186/1756-9966-32-10

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23442927


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