LSD1 binds to HPV16 E7 and promotes the epithelialmesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter

Yuan Liu; Yanan Wang; Chunqin Chen; Jiawen Zhang; Wenyan Qian; Yu Dong; Zhiqiang Liu; Xi Zhang; Xiaoyun Wang; Zhenbo Zhang; Xiaobing Shi; Sufang Wu

doi:10.18632/oncotarget.13516

LSD1 binds to HPV16 E7 and promotes the epithelialmesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter

Yuan Liu, Yanan Wang, Chunqin Chen, Jiawen Zhang, Wenyan Qian, Yu Dong, Zhiqiang Liu, Xi Zhang, Xiaoyun Wang, Zhenbo Zhang, Xiaobing Shi, Sufang Wu

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7- induced epithelial-mesenchymal transition (EMT). We proposed a novel mechanism, whereby LSD1 is recruited to the Vimentin promoter and demethylates H3K4me1 and H3K4me2. Notably, HPV16 E7 enhanced the expression of LSD1, formed a complex with LSD1, and suppressed LSD1 demethylase activity by hindering the recruitment of LSD1 to the Vimentin promoter. Thus, LSD1 is a primary and positive regulator of the HPV16 E7-induced EMT and an attractive therapeutic target for alleviating HPV16 E7-induced EMT and tumor metastasis.

Original language	English (US)
Pages (from-to)	11329-11342
Number of pages	14
Journal	Oncotarget
Volume	8
Issue number	7
DOIs	https://doi.org/10.18632/oncotarget.13516
State	Published - 2017

Keywords

Cervical cancer
EMT
HPV16E7
LSD1

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.13516

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title = "LSD1 binds to HPV16 E7 and promotes the epithelialmesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter",

abstract = "Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7- induced epithelial-mesenchymal transition (EMT). We proposed a novel mechanism, whereby LSD1 is recruited to the Vimentin promoter and demethylates H3K4me1 and H3K4me2. Notably, HPV16 E7 enhanced the expression of LSD1, formed a complex with LSD1, and suppressed LSD1 demethylase activity by hindering the recruitment of LSD1 to the Vimentin promoter. Thus, LSD1 is a primary and positive regulator of the HPV16 E7-induced EMT and an attractive therapeutic target for alleviating HPV16 E7-induced EMT and tumor metastasis.",

keywords = "Cervical cancer, EMT, HPV16E7, LSD1",

author = "Yuan Liu and Yanan Wang and Chunqin Chen and Jiawen Zhang and Wenyan Qian and Yu Dong and Zhiqiang Liu and Xi Zhang and Xiaoyun Wang and Zhenbo Zhang and Xiaobing Shi and Sufang Wu",

note = "Funding Information: The project was supported by grants from the National Natural Science Foundation of China (NSFC No.81201541, 81502230) and The Shanghai Pugiang Talent Program (12PJD002).",

year = "2017",

doi = "10.18632/oncotarget.13516",

language = "English (US)",

volume = "8",

pages = "11329--11342",

journal = "Oncotarget",

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TY - JOUR

T1 - LSD1 binds to HPV16 E7 and promotes the epithelialmesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter

AU - Liu, Yuan

AU - Wang, Yanan

AU - Chen, Chunqin

AU - Zhang, Jiawen

AU - Qian, Wenyan

AU - Dong, Yu

AU - Liu, Zhiqiang

AU - Zhang, Xi

AU - Wang, Xiaoyun

AU - Zhang, Zhenbo

AU - Shi, Xiaobing

AU - Wu, Sufang

N1 - Funding Information: The project was supported by grants from the National Natural Science Foundation of China (NSFC No.81201541, 81502230) and The Shanghai Pugiang Talent Program (12PJD002).

PY - 2017

Y1 - 2017

N2 - Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7- induced epithelial-mesenchymal transition (EMT). We proposed a novel mechanism, whereby LSD1 is recruited to the Vimentin promoter and demethylates H3K4me1 and H3K4me2. Notably, HPV16 E7 enhanced the expression of LSD1, formed a complex with LSD1, and suppressed LSD1 demethylase activity by hindering the recruitment of LSD1 to the Vimentin promoter. Thus, LSD1 is a primary and positive regulator of the HPV16 E7-induced EMT and an attractive therapeutic target for alleviating HPV16 E7-induced EMT and tumor metastasis.

AB - Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7- induced epithelial-mesenchymal transition (EMT). We proposed a novel mechanism, whereby LSD1 is recruited to the Vimentin promoter and demethylates H3K4me1 and H3K4me2. Notably, HPV16 E7 enhanced the expression of LSD1, formed a complex with LSD1, and suppressed LSD1 demethylase activity by hindering the recruitment of LSD1 to the Vimentin promoter. Thus, LSD1 is a primary and positive regulator of the HPV16 E7-induced EMT and an attractive therapeutic target for alleviating HPV16 E7-induced EMT and tumor metastasis.

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KW - EMT

KW - HPV16E7

KW - LSD1

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LSD1 binds to HPV16 E7 and promotes the epithelialmesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter

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