A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene
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-stran...
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doaj-2d9a584771c4405bb53b495e534295382020-11-25T00:09:42ZengMDPI AGMolecules1420-30492010-09-011596127613910.3390/molecules15096127A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 GeneLun-Quan SunYa CaoXiaoqian MaZhongxin LuLifang YangEpstein-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. http://www.mdpi.com/1420-3049/15/9/6127/LMP1DNAzymeNPCtargeted therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lun-Quan Sun Ya Cao Xiaoqian Ma Zhongxin Lu Lifang Yang |
spellingShingle |
Lun-Quan Sun Ya Cao Xiaoqian Ma Zhongxin Lu Lifang Yang A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene Molecules LMP1 DNAzyme NPC targeted therapy |
author_facet |
Lun-Quan Sun Ya Cao Xiaoqian Ma Zhongxin Lu Lifang Yang |
author_sort |
Lun-Quan Sun |
title |
A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene |
title_short |
A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene |
title_full |
A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene |
title_fullStr |
A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene |
title_full_unstemmed |
A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene |
title_sort |
therapeutic approach to nasopharyngeal carcinomas by dnazymes targeting ebv lmp-1 gene |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2010-09-01 |
description |
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. |
topic |
LMP1 DNAzyme NPC targeted therapy |
url |
http://www.mdpi.com/1420-3049/15/9/6127/ |
work_keys_str_mv |
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