北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学深圳医院  > 生殖医学科  > 期刊论文
学科主题: 临床医学
题名:
TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy
作者: 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
发表日期: 2015
DOI: 10.1172/JC178206
卷: 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
所属项目编号: 2015CB553903 ; 2013CB911304 ; 2009CB521806 ; 81372805 ; 81090414 ; 81301126 ; 81402158 ; 81471508 ; 81101971 ; 81402159 ; 81272859 ; 81372801 ; 81302266 ; 81372806 ; 81370469 ; 81403166 ; 81172466 ; 81101964 ; 81172468 ; 81230052 ; 81230038
项目资助者: National Development Program (973 Program) For the Key Basic Research of China ; National Natural Science Funding of China
WOS记录号: WOS:000347747300043
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58214
Appears in Collections:北京大学深圳医院_生殖医学科_期刊论文

Files in This Item:

There are no files associated with this item.


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

Recommended Citation:
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.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Hu, Zheng]'s Articles
[Ding, Wencheng]'s Articles
[Zhu, Da]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Hu, Zheng]‘s Articles
[Ding, Wencheng]‘s Articles
[Zhu, Da]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

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

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace