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Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers
Author(s) -
Hayami Shinya,
Kelly John D.,
Cho HyunSoo,
Yoshimatsu Masanori,
Unoki Motoko,
Tsunoda Tatsuhiko,
Field Helen I.,
Neal David E.,
Yamaue Hiroki,
Ponder Bruce A.J.,
Nakamura Yusuke,
Hamamoto Ryuji
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25349
Subject(s) - biology , demethylase , chromatin , carcinogenesis , chromatin remodeling , cancer research , histone , bivalent chromatin , microbiology and biotechnology , cancer , genetics , gene
A number of histone demethylases have been identified and biochemically characterized, but the pathological roles of their dysfunction in human disease like cancer have not been well understood. Here, we demonstrate important roles of lysine‐specific demethylase 1 (LSD1) in human carcinogenesis. Expression levels of LSD1 are significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues ( p < 0.0001). cDNA microarray analysis also revealed its transactivation in lung and colorectal carcinomas. LSD1‐specific small interfering RNAs significantly knocked down its expression and resulted in suppression of proliferation of various bladder and lung cancer cell lines. Concordantly, introduction of exogenous LSD1 expression promoted cell cycle progression of human embryonic kidney fibroblast cells. Expression profile analysis showed that LSD1 could affect the expression of genes involved in various chromatin‐modifying pathways such as chromatin remodeling at centromere, centromeric heterochromatin formation and chromatin assembly, indicating its essential roles in carcinogenesis through chromatin modification.