Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G1/S transition

Masaharu Kogure, Masashi Takawa, Hyun Soo Cho, Gouji Toyokawa, Kazuyuki Hayashi, Tatsuhiko Tsunoda, Takaaki Kobayashi, Yataro Daigo, Masanori Sugiyama, Yutaka Atomi, Yusuke Nakamura, Ryuji Hamamoto

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Abstract

Although a number of JmjC-containing histone demethylases have been identified and biochemically characterized, pathological roles of their dysfunction in human disease such as cancer have not been well elucidated. Here, we report the Jumonji domain containing 2A (JMJD2A) is integral to proliferation of cancer cells. Quantitative real-time PCR analysis revealed higher expression of JMJD2A in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001). Immunohistochemical analysis also showed positive staining for JMJD2A in 288 out of 403 lung cancer cases, whereas no staining was observed in lung normal tissues. Suppression of JMJD2A expression in lung and bladder cancer cells overexpressing this gene, using specific siRNAs, inhibited incorporation of BrdU and resulted in significant suppression of cell growth. Furthermore, JMJD2A appears to directly transactivate the expression of some tumor associated proteins including ADAM12 through the regulation of histone H3K9 methylation. As expression levels of JMJD2A are low in normal tissues, it may be feasible to develop specific inhibitors targeting the enzyme as anti-tumor agents which should have a minimal risk of adverse reaction.

Original languageEnglish
Pages (from-to)76-84
Number of pages9
JournalCancer Letters
Volume336
Issue number1
DOIs
Publication statusPublished - Aug 9 2013

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Jumonji Domain-Containing Histone Demethylases
Carcinogenesis
Urinary Bladder Neoplasms
Lung Neoplasms
Neoplasms
Histone Demethylases
Staining and Labeling
Enzyme Inhibitors
Bromodeoxyuridine
Histones
Methylation
Real-Time Polymerase Chain Reaction
Cell Proliferation
Lung
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G1/S transition. / Kogure, Masaharu; Takawa, Masashi; Cho, Hyun Soo; Toyokawa, Gouji; Hayashi, Kazuyuki; Tsunoda, Tatsuhiko; Kobayashi, Takaaki; Daigo, Yataro; Sugiyama, Masanori; Atomi, Yutaka; Nakamura, Yusuke; Hamamoto, Ryuji.

In: Cancer Letters, Vol. 336, No. 1, 09.08.2013, p. 76-84.

Research output: Contribution to journalArticle

Kogure, M, Takawa, M, Cho, HS, Toyokawa, G, Hayashi, K, Tsunoda, T, Kobayashi, T, Daigo, Y, Sugiyama, M, Atomi, Y, Nakamura, Y & Hamamoto, R 2013, 'Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G1/S transition', Cancer Letters, vol. 336, no. 1, pp. 76-84. https://doi.org/10.1016/j.canlet.2013.04.009
Kogure, Masaharu ; Takawa, Masashi ; Cho, Hyun Soo ; Toyokawa, Gouji ; Hayashi, Kazuyuki ; Tsunoda, Tatsuhiko ; Kobayashi, Takaaki ; Daigo, Yataro ; Sugiyama, Masanori ; Atomi, Yutaka ; Nakamura, Yusuke ; Hamamoto, Ryuji. / Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G1/S transition. In: Cancer Letters. 2013 ; Vol. 336, No. 1. pp. 76-84.
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