Document Detail


Misprocessing and functional arrest of microRNAs by miR-Pirate, roles of miR-378 in vitro and in vivo.
MedLine Citation:
PMID:  23210454     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
MicroRNAs are short non-coding RNAs that can regulate gene expression in cancer development, which makes them valuable targets for therapeutic intervention. Here we report on an approach that can not only arrest the functions of mature miRNAs by binding to them but it can also induce the "mis-processing" of the target miRNA producing a non-functional truncated miRNA. This approach involves generating an expression construct that produces a RNA fragment with sixteen repeat sequences. The construct is named miR-Pirate or microRNA-interacting RNA-producing imperfect RNA and tangling endogenous miRNA. The transcript of the construct contained mismatches to the seed region, and thus it would not target the potential targets of the miRNA under study. The homology of the construct is sufficiently high allowing the transcript to block miRNA functions. The functions of the construct were validated in cell cultures, in tumor formation assays, and in transgenic mice stably expressing this construct. To explore the possibility of adopting this approach in gene therapy, we transfected cells with synthetic miR-Pirate and obtained the results we expected. The miR-Pirate, expressed by the construct or synthesized chemically, was found to be able to specifically pirate and silence a mature miRNA through its dual roles and thus could be clinically applied for miRNA intervention.
Authors:
Zhaoqun Deng; Xiangling Yang; Ling Fang; Zina Jeyapalan Rutnam; Burton B Yang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-5
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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