Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells

doi:10.3389/fcell.2021.677867

科研成果详情

题名	Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells
作者	Zhu, Jinshun1,2; Kamara, Saidu 1; Wang, Qi 1; Guo, Yanru 1; Li, Qingfeng 1; Wang, Linlin2; Chen, Jingjing 1; Du, Qianqian 1; Du, Wangqi1; Chen, Shao1; Zhu, Shanli1; Chen, Jun1; Chu, Maoping2; Zhang, Lifang1
发表日期	2021-05-24
发表期刊	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	HPV oncoprotein E6 affibody molecules cervical cancer molecular imaging targeted therapy
其他关键词	ANTIBODY FRAGMENTS ; IN-VITRO ; THERAPY ; DEGRADATION ; SELECTION ; PEPTIDES
摘要	Despite prophylactic vaccination campaigns, high-risk human papillomavirus (HPV)-induced cervical cancer remains a significant health threat among women, especially in developing countries. The initial occurrence and consequent progression of this cancer type primarily rely on, E6 and E7, two key viral oncogenes expressed constitutively, inducing carcinogenesis. Thus, E6/E7 have been proposed as ideal targets for HPV-related cancer diagnosis and treatment. In this study, three novel HPV16 E6-binding affibody molecules (Z(HPV16E6)1115, Z(HPV16E6)1171, and Z(HPV16E6)1235) were isolated from a randomized phage display library and cloned for bacterial production. These affibody molecules showed high binding affinity and specificity for recombinant and native HPV16 E6 as determined by surface plasmon resonance, indirect immunofluorescence, immunohistochemistry, and near-infrared small animal optical imaging in vitro and in vivo. Moreover, by binding to HPV16 E6 protein, Z(HPV16E6)1235 blocked E6-mediated p53 degradation, which increased the expression of some key p53 target genes, including BAX, PUMA and p21, and thereby selectively reduced the viability and proliferation of HPV16-positive cells. Importantly, Z(HPV16E6)1235 was applied in combination with HPV16 E7-binding affibody Z(HPV16E7)384 to simultaneously target the HPV16 E6/E7 oncoproteins, and this combination inhibited cell proliferation more potently than either modality alone. Mechanistic studies revealed that the synergistic antiproliferative activity depends primarily on the induction of cell apoptosis and senescence but not cell cycle arrest. Our findings provide strong evidence that three novel HPV16 E6-binding affibody molecules could form a novel basis for the development of rational strategies for molecular imaging and targeted therapy in HPV16-positive preneoplastic and neoplastic lesions.
资助项目	National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972550, 81372447]; Public Welfare Foundation of Zhejiang Province [LGF19H160023]; Wenzhou Science and Technology Bureau of China [Y20180072]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	2296-634X
卷号	9 页码:677867
DOI	10.3389/fcell.2021.677867
页数	14
WOS类目	Cell Biology ; Developmental Biology
WOS研究方向	Cell Biology ; Developmental Biology
WOS记录号	WOS:000658323700001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	34109181
PMC记录号	PMC8181454
SCOPUSEID	2-s2.0-85107392598
通讯作者地址	[Zhang, Lifang]Department of Microbiology and Immunology,Institute of Molecular Virology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,China ; [Chu, Maoping]Children’s Heart Center,Institute of Cardiovascular Development and Translational Medicine,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Developmental Biology;Cell Biology
引用统计	被引频次：5[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/14783
专题	基础医学院（机能实验教学中心）_病原生物学与免疫学系第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Chu, Maoping; Zhang, Lifang
作者单位	1.Department of Microbiology and Immunology,Institute of Molecular Virology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,China; 2.Children’s Heart Center,Institute of Cardiovascular Development and Translational Medicine,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,China
第一作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系; 第二临床医学院，附属第二医院、育英儿童医院
通讯作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系; 第二临床医学院，附属第二医院、育英儿童医院
第一作者的第一单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
推荐引用方式 GB/T 7714	Zhu, Jinshun,Kamara, Saidu,Wang, Qi,et al. Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2021,9:677867.
APA	Zhu, Jinshun., Kamara, Saidu., Wang, Qi., Guo, Yanru., Li, Qingfeng., ... & Zhang, Lifang. (2021). Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 9, 677867.
MLA	Zhu, Jinshun,et al."Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9(2021):677867.