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

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302 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
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Hayami, S., Kelly, J. D., Cho, H. S., Yoshimatsu, M., Unoki, M., Tsunoda, T., Field, H. I., Neal, D. E., Yamaue, H., Ponder, B. A. J., Nakamura, Y., & Hamamoto, R. (2011). Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. International Journal of Cancer, 128(3), 574-586. https://doi.org/10.1002/ijc.25349