Document Detail

Therapeutic effects of microRNA-582-5p and -3p on the inhibition of bladder cancer progression.
MedLine Citation:
PMID:  23295946     Owner:  NLM     Status:  MEDLINE    
Many reports have indicated that the abnormal expression of microRNAs (miRNAs) is associated with the progression of disease and have identified miRNAs as attractive targets for therapeutic intervention. However, the bifunctional mechanisms of miRNA guide and passenger strands in RNA interference (RNAi) therapy have not yet been clarified. Here, we show that miRNA (miR)-582-5p and -3p, which are strongly decreased in high-grade bladder cancer clinical samples, regulate tumor progression in vitro and in vivo. Significantly, the overexpression of miR-582-5p or -3p reduced the proliferation and invasion of UM-UC-3 human bladder cancer cells. Furthermore, transurethral injections of synthetic miR-582 molecule suppressed tumor growth and metastasis in an animal model of bladder cancer. Most interestingly, our study revealed that both strands of miR-582-5p and -3p suppressed the expression of the same set of target genes such as protein geranylgeranyltransferase type I beta subunit (PGGT1B), leucine-rich repeat kinase 2 (LRRK2) and DIX domain containing 1 (DIXDC1). Knockdown of these genes using small interfering RNA (siRNA) resulted in the inhibition of cell growth and invasiveness of UM-UC-3. These findings uncover the unique regulatory pathway involving tumor suppression by both strands of a single miRNA that is a potential therapeutic target in the treatment of invasive bladder cancer.
Keita Uchino; Fumitaka Takeshita; Ryou-U Takahashi; Nobuyoshi Kosaka; Kae Fujiwara; Haruna Naruoka; Satoru Sonoke; Junichi Yano; Hideo Sasaki; Shiari Nozawa; Miki Yoshiike; Kazuki Kitajima; Tatsuya Chikaraishi; Takahiro Ochiya
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-08
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  21     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-01     Completed Date:  2013-10-22     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  610-9     Citation Subset:  IM    
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MeSH Terms
Alkyl and Aryl Transferases / genetics,  metabolism
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Disease Progression
Gene Expression Regulation, Neoplastic*
Genetic Therapy
Intracellular Signaling Peptides and Proteins / genetics,  metabolism
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics,  therapeutic use*
Microfilament Proteins / genetics,  metabolism
Protein-Serine-Threonine Kinases / genetics,  metabolism
RNA Interference
RNA, Small Interfering / genetics
Urinary Bladder Neoplasms / genetics*,  pathology,  therapy*
Reg. No./Substance:
0/DIXDC1 protein, human; 0/Intracellular Signaling Peptides and Proteins; 0/MicroRNAs; 0/Microfilament Proteins; 0/RNA, Small Interfering; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.-/geranylgeranyltransferase type-I; EC protein, human; EC Kinases

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