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学科主题临床医学
TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy
Hu, Zheng1; Ding, Wencheng1; Zhu, Da1; Yu, Lan1; Jiang, Xiaohui1; Wang, Xiaoli1; Zhang, Changlin1; Wang, Liming1; Ji, Teng1; Liu, Dan1; He, Dan2; Xia, Xi3; Zhu, Tao1; Wei, Juncheng1; Wu, Peng1; Wang, Changyu1; Xi, Ling1; Gao, Qinglei1; Chen, Gang1; Liu, Rong1; Li, Kezhen1; Li, Shuang1; Wang, Shixuan1; Zhou, Jianfeng1; Ma, Ding1; Wang, Hui1
刊名JOURNAL OF CLINICAL INVESTIGATION
2015
DOI10.1172/JC178206
125期:1页:425-436
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental
研究领域[WOS]Research & Experimental Medicine
关键词[WOS]HUMAN-PAPILLOMAVIRUS TYPE-16 ; ZINC-FINGER NUCLEASES ; CANCER CELLS ; CAS9 ; E6 ; SPECIFICITY ; ASSOCIATION ; PREVENTION ; NEOPLASIA ; EFFECTORS
英文摘要

Persistent HPV infection is recognized as the main etiologic factor for cervical cancer. HPV expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. While siRNA-mediated targeting of E6 and E7 transcripts temporarily induces apoptosis in HPV-positive cells, it does not eliminate viral DNA within the host genome, which can harbor escape mutants. Here, we demonstrated that specifically targeting E6 and E7 within host DNA with transcription activator-like effector nucleases (TALENs) induces apoptosis, inhibits growth, and reduces tumorigenicity in HPV-positive cell lines. TALEN treatment efficiently disrupted E6 and E7 oncogenes, leading to the restoration of host tumor suppressors p53 and retinoblastoma 1 (RB1), which are targeted by E6 and E7, respectively. In the K14-HPV16 transgenic mouse model of HPV-driven neoplasms, direct cervical application of HPV16-E7-targeted TALENs effectively mutated the E7 oncogene, reduced viral DNA load, and restored RB1 function and downstream targets transcription factor E2F1 and cycling-dependent kinase 2 (CDK2), thereby reversing the malignant phenotype. Together, the results from our study suggest that TALENs have potential as a therapeutic strategy for HPV infection and related cervical malignancy.

语种英语
WOS记录号WOS:000347747300043
项目编号2015CB553903 ; 2013CB911304 ; 2009CB521806 ; 81372805 ; 81090414 ; 81301126 ; 81402158 ; 81471508 ; 81101971 ; 81402159 ; 81272859 ; 81372801 ; 81302266 ; 81372806 ; 81370469 ; 81403166 ; 81172466 ; 81101964 ; 81172468 ; 81230052 ; 81230038
资助机构National Development Program (973 Program) For the Key Basic Research of China ; National Natural Science Funding of China
引用统计
被引频次:26[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/400002259/58214
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 Hosp, Tongji Med Coll, Canc Biol Res Ctr, Wuhan 430030, Hubei, Peoples R China
2.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Neurol, Wuhan 430030, Hubei, Peoples R China
3.Peking Univ, Shenzhen Hosp, Ctr Reprod Med, Shenzhen, Guangdong, Peoples R China
推荐引用方式
GB/T 7714
Hu, Zheng,Ding, Wencheng,Zhu, Da,et al. TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy[J]. JOURNAL OF CLINICAL INVESTIGATION,2015,125(1):425-436.
APA Hu, Zheng.,Ding, Wencheng.,Zhu, Da.,Yu, Lan.,Jiang, Xiaohui.,...&Wang, Hui.(2015).TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy.JOURNAL OF CLINICAL INVESTIGATION,125(1),425-436.
MLA Hu, Zheng,et al."TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy".JOURNAL OF CLINICAL INVESTIGATION 125.1(2015):425-436.
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