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Attenuation of telomerase activity by hammerhead ribozyme targeting human telomerase RNA induces growth retardation and apoptosis in human breast tumor cells

Authors
 Marie Yeo  ;  Sung Young Rha  ;  Hei Cheul Jeung  ;  Shen Xiong Hu  ;  Sang Hwa Yang  ;  Yang Seok Kim  ;  Sung Whan An  ;  Hyun Cheol Chung 
Citation
 International Journal of Cancer, Vol.114(3) : 484-489, 2005 
Journal Title
 International Journal of Cancer 
ISSN
 0020-7136 
Issue Date
2005
MeSH
Apoptosis* ; Breast Neoplasms/pathology* ; Cell Proliferation ; Female ; Humans ; RNA/biosynthesis ; RNA/metabolism* ; RNA, Catalytic/pharmacology* ; Telomerase/pharmacology* ; Transfection ; Tumor Cells, Cultured
Keywords
ribozyme ; telomere ; telomerase ; human telomerase reverse transcriptase ; human telomerase RNA component
Abstract
Ribozyme possesses specific endoribonuclease activity and catalyzes the hydrolysis of specific phosphodiester bonds, which results in the cleavage of target RNA sequences. Here, we evaluated the ability of hammerhead ribozymes targeting human telomerase RNA (hTR) to inhibit the catalytic activity of telomerase and the proliferation of cancer cells. Hammerhead ribozymes were designed against 7 NUX sequences located in open loops of the hTR secondary structure. We verified the ribozyme specificity by in vitro cleavage assay by using a synthetic RNA substrate. Subsequently, we introduced ribozyme expression vector into human breast tumor MCF-7 cells and assessed the biologic effects of ribozyme. Hammerhead ribozyme R1 targeting the template region of hTR efficiently cleaved hTR in vitro, and stable transfectants of this ribozyme induced the degradation of target hTR RNA and attenuated telomerase activity in MCF-7 cells. Moreover, the ribozyme R1 transfectant displayed a significant telomere shortening and a lower proliferation rate than parental cells. Clones with reduced proliferation capacity showed enlarged senescence-like shapes or highly differentiated dendritic morphologies of apoptosis. In conclusion, the inhibition of telomerase activity by hammerhead ribozyme targeting the template region of the hTR presents a promising strategy for inhibiting the growth of human breast cancer cells.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/ijc.20720/abstract
DOI
10.1002/ijc.20720
Appears in Collections:
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yang Seok(김양석)
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Shen, Xiong Hu(심웅호)
An, Sung Whan(안성환)
Yang, Sang Hwa(양상화)
Yeo, Marie(여말희)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/150783
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