Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers

Shinya Hayami, John D. Kelly, Hyun Soo Cho, Masanori Yoshimatsu, Motoko Unoki, Tatsuhiko Tsunoda, Helen I. Field, David E. Neal, Hiroki Yamaue, Bruce A.J. Ponder, Yusuke Nakamura, Ryuji Hamamoto

    Research output: Contribution to journalArticle

    280 Citations (Scopus)

    Abstract

    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 languageEnglish
    Pages (from-to)574-586
    Number of pages13
    JournalInternational Journal of Cancer
    Volume128
    Issue number3
    DOIs
    Publication statusPublished - Feb 1 2011

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    Lysine
    Chromatin
    Carcinogenesis
    Chromatin Assembly and Disassembly
    Neoplasms
    Urinary Bladder
    Histone Demethylases
    Heterochromatin
    Centromere
    Microarray Analysis
    Oligonucleotide Array Sequence Analysis
    Urinary Bladder Neoplasms
    Small Interfering RNA
    Transcriptional Activation
    Colorectal Neoplasms
    Lung Neoplasms
    Cell Cycle
    Fibroblasts
    Carcinoma
    Kidney

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

    Cite this

    Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. / Hayami, Shinya; Kelly, John D.; Cho, Hyun Soo; Yoshimatsu, Masanori; Unoki, Motoko; Tsunoda, Tatsuhiko; Field, Helen I.; Neal, David E.; Yamaue, Hiroki; Ponder, Bruce A.J.; Nakamura, Yusuke; Hamamoto, Ryuji.

    In: International Journal of Cancer, Vol. 128, No. 3, 01.02.2011, p. 574-586.

    Research output: Contribution to journalArticle

    Hayami, S, Kelly, JD, Cho, HS, Yoshimatsu, M, Unoki, M, Tsunoda, T, Field, HI, Neal, DE, Yamaue, H, Ponder, BAJ, Nakamura, Y & Hamamoto, R 2011, 'Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers', International Journal of Cancer, vol. 128, no. 3, pp. 574-586. https://doi.org/10.1002/ijc.25349
    Hayami, Shinya ; Kelly, John D. ; Cho, Hyun Soo ; Yoshimatsu, Masanori ; Unoki, Motoko ; Tsunoda, Tatsuhiko ; Field, Helen I. ; Neal, David E. ; Yamaue, Hiroki ; Ponder, Bruce A.J. ; Nakamura, Yusuke ; Hamamoto, Ryuji. / Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. In: International Journal of Cancer. 2011 ; Vol. 128, No. 3. pp. 574-586.
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