title: Overexpression of lysine-specific demethylase 1 promotes androgen-independent transition of human prostate cancer LNCaP cells through activation of the AR signaling pathway and suppression of the p53 signaling pathway.
abstract: Lysine-specific demethylase 1 (LSD1) is the first defined histone demethylase, and was found to be closely correlated with the development and progression of various types of cancers, including prostate cancer (PCa). Previous research suggests that LSD1 is closely related with cell proliferation, angiogenesis, migration and invasion in PCa. However, it remains to be elucidated whether LSD1 is correlated with androgen-independent (AI) transition of PCa under androgen-ablated conditions. The present study aimed to investigate the correlation of LSD1 expression with AI transition of human androgen-dependent PCa LNCaP cells. Our data showed that LSD1 was overexpressed in human PCa specimens and in AI PCa LNCaP-AI cells, which were established through a three-month continuous culture of LNCaP cells in androgen-deprived medium. Under androgen-deprived conditions, LNCaP-AI cells grew perfectly with less apoptosis and G0/G1 cell cycle arrest. Overexpression of LSD1 protected the LNCaP cells from androgen deprivation-induced apoptosis and G0/G1 arrest, while knockdown of LSD1 drove LNCaP-AI cells into a higher rate of apoptosis and G0/G1 arrest. Furthermore, LSD1 was found to regulate the androgen receptor (AR) and p53 signaling pathways via demethylation, subsequently influencing apoptosis and cell cycle progression. These findings revealed that overexpression of LSD1 promoted AI transition of PCa LNCaP cells under androgen-ablated conditions via activation of the AR signaling pathway and suppression of the p53 signaling pathway.
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Urology, Xiangyang Central Hospital, Xiangyang, Hubei 441021, P.R. China.
authors.forename: Dehong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Hongxue
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Xing
mesh_terms: D000728:Androgens / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D000728:Androgens; D011944:Receptors, Androgen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D056466:Histone Demethylases; C495195:KDM1A protein, human