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

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Title
Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G1/S transition
Author(s)
M Kogure; M Takawa; Hyun Soo Cho; G Toyokawa; K Hayashi; T Tsunoda; T Kobayashi; Y Daigo; M Sugiyama; Y Atomi; Y Nakamura; R Hamamoto
Bibliographic Citation
Cancer Letters, vol. 336, no. 1, pp. 76-84
Publication Year
2013
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.
Keyword
G1/S transitionHistone demethylaseHuman carcinogenesisJMJD2A
ISSN
0304-3835
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.canlet.2013.04.009
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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