Lysine-specific demethylase 1 (LSD1) promotes ovarian cancer cell progression by Forkhead box O 3a (FOXO3a) inhibition

Recently, LSD1 is considered as a possible therapeutic mark for ovarian epithelial cancer (OEC). Though, the underlying molecular mechanism by which LSD1 endorses the oncogenesis of OEC has not been fully understood. Here, we revealed that overexpression of LSD1 downregulated Forkhead box O 3a (FOXO...

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Bibliographic Details
Published in:Materials express 2020-04, Vol.10 (4), p.594-602
Main Authors: Liu, Li, Hao, Fuxing, Wang, Anping, Chen, Xiaolan, Zhang, Bin, Wu, Zhi, Wang, Yongjuan, Wu, Shuang, Liu, Ting, Ma, Songbo
Format: Article
Language:English
Subjects:
Cancer
Cell growth
Demethylation
Foxo3a
Lsd1
Lysine
Ovarian Cancer
Proliferation
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Summary:Recently, LSD1 is considered as a possible therapeutic mark for ovarian epithelial cancer (OEC). Though, the underlying molecular mechanism by which LSD1 endorses the oncogenesis of OEC has not been fully understood. Here, we revealed that overexpression of LSD1 downregulated Forkhead box O 3a (FOXO3a), while knockdown or pharmacological inhibition of LSD1 upregulated FOXO3a expression. Specifically, LSD1 interacted with demethylated FOXO3a. The LSD1-demethylated FOXO3a degraded via an ubiquitin-proteasome pathway. Biologically, LSD1 destabilized FOXO3a to abrogate its functions in the suppression of soft agar colony and cell proliferation formation in HO8910 ovarian cancer cells. Knockdown of FOXO3a rescued the restricted cell proliferation by LSD1 downregulation. As a whole, our study clarifies a way in ovarian cancer cell growth through the negative regulation of FOXO3a by LSD1.
ISSN:2158-5849
2158-5857
DOI:10.1166/mex.2020.1674