0 117

Cited 38 times in

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

 Marie Yeo  ;  Sung Young Rha  ;  Hei Cheul Jeung  ;  Shen Xiong Hu  ;  Sang Hwa Yang  ;  Yang Seok Kim  ;  Sung Whan An  ;  Hyun Cheol Chung 
 International Journal of Cancer, Vol.114(3) : 484-489, 2005 
Journal Title
 International Journal of Cancer 
Issue Date
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
Appears in Collections:
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
김양석(Kim, Yang Seok)
라선영(Rha, Sun Young)
심웅호(Shen, Xiong Hu)
안성환(An, Sung Whan)
양상화(Yang, Sang Hwa)
여말희(Yeo, Marie)
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
정희철(Jeung, Hei Cheul)
RIS (EndNote)
XLS (Excel)
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.