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Zinc Finger Nucleases Targeting the Human Papillomavirus E7 Oncogene Induce E7 Disruption and a Transformed Phenotype in HPV16/18-Positive Cervical Cancer Cells
Ding, Wencheng1; Hu, Zheng1; Zhu, Da1; Jiang, Xiaohui1; Yu, Lan1; Wang, Xiaoli1; Zhang, Changlin1; Wang, Liming1; Ji, Teng1; Li, Kezhen1; He, Dan2; Xia, Xi3; Liu, Dan1; Zhou, Jianfeng4; Ma, Ding1; Wang, Hui1
刊名CLINICAL CANCER RESEARCH
2014-12-15
DOI10.1158/1078-0432.CCR-14-0250
20期:24页:6495-6503
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]RNA-INTERFERENCE ; T-CELLS ; GENE ; E6 ; TYPE-16 ; GENERATION ; WORLDWIDE ; KNOCKOUT ; CASKI ; DNA
英文摘要

Purpose: Cervical cancer is mainly caused by infections of high-risk human papillomavirus (HR-HPV). Persistent expression of HR-HPV oncogenes E6 and E7 is implicated in malignant transformation. The aim was to provide proof-of-concept data to support use of zinc finger nucleases (ZFN) targeting HPV E7 to treat HPV-related cervical cancer.

Experimental Design: We designed and constructed ZFNs that could specifically recognize and cleave HPV16/18 E7 DNA. We tested the cleavage efficiency of selected ZFN16-E7-S2 and ZFN18-E7-S2 by using single-strand annealing (SSA) assay. Cell viability and colony formation assays were used to estimate the inhibition of cell growth that received treatments of ZFNs. Gene disruption of HPV E7 and downstream genes were examined by Western blotting. Cell apoptosis assay was used to test the specificity and efficiency of induction of HPV type-specific apoptosis. We also introduced xenograft formation assays to estimate the potential of inhibition of HPV-related disease.

Results: We found ZFN16-E7-S2 and ZFN18-E7-S2 disrupted HPV E7 oncogenes in HPV16/18-positive cervical cancer cells. Both ZFNs effectively led to inhibition of type-specific cervical cancer cell growth, and specifically induced apoptosis of corresponding HPV16-and HPV18-positive cervical cancer cell lines. ZFN16-E7-S2 and ZFN18-E7-S2 also repressed xenograft formation in vivo.

Conclusion: ZFNs targeting HPV16/18 E7 could effectively induce disruption of E7 oncogenes and lead to type-specific and efficient growth inhibition and apoptosis of HPV-positive cells. ZFNs targeting HPV16/ 18 E7 oncogenes could be used as novel therapeutic agents for the treatment of HPV-related cervical cancer. (C) 2014 AACR.

语种英语
WOS记录号WOS:000346418100029
项目编号2015CB553903 ; 2009CB521800 ; 2013CB911304 ; 2009CB521806 ; 81372805 ; 81090414 ; 81402158 ; 81471508 ; 81101971 ; 81402159 ; 81301126 ; 81302266
资助机构National Development Program (973) for Key Basic Research of China ; National Natural Science Funding of China (NSFC
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51840
专题北京大学深圳医院_生殖医学科
作者单位1.Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Obstet & Gynecol, Wuhan 430030, Hubei, Peoples R China
2.Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Neurol, Wuhan 430030, Hubei, Peoples R China
3.Peking Univ, Shenzhen Hosp, Ctr Reprod Med, Shenzhen, Guangdong, Peoples R China
4.Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Hematol, Wuhan 430030, Hubei, Peoples R China
推荐引用方式
GB/T 7714
Ding, Wencheng,Hu, Zheng,Zhu, Da,et al. Zinc Finger Nucleases Targeting the Human Papillomavirus E7 Oncogene Induce E7 Disruption and a Transformed Phenotype in HPV16/18-Positive Cervical Cancer Cells[J]. CLINICAL CANCER RESEARCH,2014,20(24):6495-6503.
APA Ding, Wencheng.,Hu, Zheng.,Zhu, Da.,Jiang, Xiaohui.,Yu, Lan.,...&Wang, Hui.(2014).Zinc Finger Nucleases Targeting the Human Papillomavirus E7 Oncogene Induce E7 Disruption and a Transformed Phenotype in HPV16/18-Positive Cervical Cancer Cells.CLINICAL CANCER RESEARCH,20(24),6495-6503.
MLA Ding, Wencheng,et al."Zinc Finger Nucleases Targeting the Human Papillomavirus E7 Oncogene Induce E7 Disruption and a Transformed Phenotype in HPV16/18-Positive Cervical Cancer Cells".CLINICAL CANCER RESEARCH 20.24(2014):6495-6503.
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