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Molecules 2010, 15(9), 6127-6139; doi:10.3390/molecules15096127

A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene

1, 1, 1,*  and 2,3,*
1 Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China 2 Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China 3 Department of Medical and Molecular Biosciences, University of Technology Sydney, Australia
* Authors to whom correspondence should be addressed.
Received: 18 June 2010 / Revised: 26 August 2010 / Accepted: 30 August 2010 / Published: 1 September 2010
(This article belongs to the Special Issue Catalytic Nucleic Acids)
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Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) has been known to have oncogenic properties during latent infection in nasopharyngeal carcinoma (NPC). Genetic manipulation of LMP1 expression may provide a novel strategy for the treatment of NPC. DNAzymes are synthetic, single-stranded DNA catalysts that can be engineered to bind and cleave the target mRNA of a disease-causing gene. By targeting the LMP1 mRNA, we successfully obtained a phosphorothioate-modified ‘‘10–23’’ DNAzyme namely DZ1, through screening a series of DNAzymes. DZ1 could significantly down-regulate the expression of LMP1 in NPC cells, inhibit cell proliferation, metastasis, promote apoptosis and enhance radiosensitivity of NPC through interfering signal pathways which are abnormally activated by LMP1, including NF-κB, AP-1 and STAT3 signal pathways. Together, interfering LMP1 signaling pathway could be a promising strategy to target the malignant phenotypes of NPC.
Keywords: LMP1; DNAzyme; NPC; targeted therapy LMP1; DNAzyme; NPC; targeted therapy
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Yang, L.; Lu, Z.; Ma, X.; Cao, Y.; Sun, L.-Q. A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene. Molecules 2010, 15, 6127-6139.

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