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*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 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 languageEnglish (US)
Pages (from-to)11329-11342
Number of pages14
JournalOncotarget
Volume8
Issue number7
DOIs
StatePublished - 2017

Keywords

  • Cervical cancer
  • EMT
  • HPV16E7
  • LSD1

ASJC Scopus subject areas

  • Oncology

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    Liu, Y., Wang, Y., Chen, C., Zhang, J., Qian, W., Dong, Y., Liu, Z., Zhang, X., Wang, X., Zhang, Z., Shi, X., & Wu, S. (2017). LSD1 binds to HPV16 E7 and promotes the epithelialmesenchymal transition in cervical cancer by demethylating histones at the Vimentin promoter. Oncotarget, 8(7), 11329-11342. https://doi.org/10.18632/oncotarget.13516