LSD1-mediated epigenetic modification contributes to ovarian cancer cell migration and invasion.
Lysine-specific demethylase 1 (LSD1) has been implicated in the process of tumor progression at various steps, but its role in epithelial-messenchymal transition (EMT) and the migration of ovarian cancer cells remains obscure. In this study, we demonstrated the effect of LSD1 on ovarian cancer cell migration and the regulatory role of LSD1 in the expression of EMT markers. Inhibition of LSD1 expression impaired the migration and invasion of HO8910 ovarian cancer cells. In contrast, overexpression of LSD1 enhanced the cell migration and invasion of HO8910 cells. Mechanistic analyses showed that LSD1 promoted cell migration through induction of N-cadherin, vimentin, MMP-2 and inhibition of E-cadherin. Furthermore, LSD1 interacted with the promoter of E-cadherin and demethylated histone H3 lysine 4 (H3K4) at this region, downregulated E-cadherin expression, and consequently enhanced ovarian cancer cell migration. These data indicate that LSD1 acts as an epigenetic regulator of EMT and contributes to the metastasis of ovarian cancer.
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Yuanxia
Y
Li
Department of Oncology, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
Xiaolei
X
Wan
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Ye
Y
Wei
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Xiuwen
X
Liu
Department of General Medicine, The Affiliated Third People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212005, P.R. China.
Wensheng
W
Lai
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Liuping
L
Zhang
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Jie
J
Jin
Department of Oncology, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
Chaoyang
C
Wu
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Qixiang
Q
Shao
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Genbao
G
Shao
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Qiong
Q
Lin
D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*
D015820:Cadherins; D006657:Histones; D056466:Histone Demethylases; C495195:KDM1A protein, human