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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.

Original publication

DOI

10.1002/ijc.25349

Type

Journal article

Journal

Int J Cancer

Publication Date

01/02/2011

Volume

128

Pages

574 - 586

Keywords

Cell Cycle, Cell Division, Cell Line, Tumor, Chromatin, DNA, Complementary, DNA, Neoplasm, Gene Expression Profiling, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Histone Demethylases, Humans, Immunohistochemistry, Neoplasms, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Urinary Bladder, Urinary Bladder Neoplasms