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Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway

Background: Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethyla...

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Main Authors: Hayami, Shinya, Yoshimatsu, Masanori, Veerakumarasivam, Abhimanyu, Unoki, Motoko, Iwai, Yukiko, Tsunoda, Tatsuhiko, Field, Helen I., Kelly, John D ., Neal, David E., Yamaue, Hiroki, Ponder, Bruce A. J., Nakamura, Yusuke, Hamamoto, Ryuji
Format: Article
Language:English
Published: BioMed Central 2010
Online Access:http://psasir.upm.edu.my/id/eprint/40048/1/Overexpression%20of%20the%20JmjC%20histone.pdf
http://psasir.upm.edu.my/id/eprint/40048/
http://www.molecular-cancer.com/content/9/1/59/abstract
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spelling my.upm.eprints.400482015-08-27T01:57:51Z http://psasir.upm.edu.my/id/eprint/40048/ Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway Hayami, Shinya Yoshimatsu, Masanori Veerakumarasivam, Abhimanyu Unoki, Motoko Iwai, Yukiko Tsunoda, Tatsuhiko Field, Helen I. Kelly, John D . Neal, David E. Yamaue, Hiroki Ponder, Bruce A. J. Nakamura, Yusuke Hamamoto, Ryuji Background: Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethylase, in human carcinogenesis. Quantitative RT-PCR and microarray analyses were used to examine the expression profiles of histone demethylases in clinical tissue samples. We also examined the functional effects of KDM5B on the growth of cancer cell lines treated with small interfering RNAs (siRNAs). Downstream genes and signal cascades induced by KDM5B expression were identified from Affymetrix Gene Chip experiments, and validated by real-time PCR and reporter assays. Cell cycle-dependent characteristics of KDM5B were identified by immunofluorescence and FACS. Results: Quantitative RT-PCR analysis confirmed that expression levels of KDM5B are significantly higher in human bladder cancer tissues than in their corresponding non-neoplastic bladder tissues (P < 0.0001). The expression profile analysis of clinical tissues also revealed up-regulation of KDM5B in various kinds of malignancies. Transfection of KDM5B-specific siRNA into various bladder and lung cancer cell lines significantly suppressed the proliferation of cancer cells and increased the number of cells in sub-G1phase. Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. Conclusions: Inhibition of KDM5B may affect apoptosis and reduce growth of cancer cells. Further studies will explore the pan-cancer therapeutic potential of KDM5B inhibition. BioMed Central 2010-03 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/40048/1/Overexpression%20of%20the%20JmjC%20histone.pdf Hayami, Shinya and Yoshimatsu, Masanori and Veerakumarasivam, Abhimanyu and Unoki, Motoko and Iwai, Yukiko and Tsunoda, Tatsuhiko and Field, Helen I. and Kelly, John D . and Neal, David E. and Yamaue, Hiroki and Ponder, Bruce A. J. and Nakamura, Yusuke and Hamamoto, Ryuji (2010) Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway. Molecular Cancer, 9. art. no. 59. pp. 1-14. ISSN 1476-4598 http://www.molecular-cancer.com/content/9/1/59/abstract 10.1186/1476-4598-9-59
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Background: Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethylase, in human carcinogenesis. Quantitative RT-PCR and microarray analyses were used to examine the expression profiles of histone demethylases in clinical tissue samples. We also examined the functional effects of KDM5B on the growth of cancer cell lines treated with small interfering RNAs (siRNAs). Downstream genes and signal cascades induced by KDM5B expression were identified from Affymetrix Gene Chip experiments, and validated by real-time PCR and reporter assays. Cell cycle-dependent characteristics of KDM5B were identified by immunofluorescence and FACS. Results: Quantitative RT-PCR analysis confirmed that expression levels of KDM5B are significantly higher in human bladder cancer tissues than in their corresponding non-neoplastic bladder tissues (P < 0.0001). The expression profile analysis of clinical tissues also revealed up-regulation of KDM5B in various kinds of malignancies. Transfection of KDM5B-specific siRNA into various bladder and lung cancer cell lines significantly suppressed the proliferation of cancer cells and increased the number of cells in sub-G1phase. Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. Conclusions: Inhibition of KDM5B may affect apoptosis and reduce growth of cancer cells. Further studies will explore the pan-cancer therapeutic potential of KDM5B inhibition.
format Article
author Hayami, Shinya
Yoshimatsu, Masanori
Veerakumarasivam, Abhimanyu
Unoki, Motoko
Iwai, Yukiko
Tsunoda, Tatsuhiko
Field, Helen I.
Kelly, John D .
Neal, David E.
Yamaue, Hiroki
Ponder, Bruce A. J.
Nakamura, Yusuke
Hamamoto, Ryuji
spellingShingle Hayami, Shinya
Yoshimatsu, Masanori
Veerakumarasivam, Abhimanyu
Unoki, Motoko
Iwai, Yukiko
Tsunoda, Tatsuhiko
Field, Helen I.
Kelly, John D .
Neal, David E.
Yamaue, Hiroki
Ponder, Bruce A. J.
Nakamura, Yusuke
Hamamoto, Ryuji
Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway
author_facet Hayami, Shinya
Yoshimatsu, Masanori
Veerakumarasivam, Abhimanyu
Unoki, Motoko
Iwai, Yukiko
Tsunoda, Tatsuhiko
Field, Helen I.
Kelly, John D .
Neal, David E.
Yamaue, Hiroki
Ponder, Bruce A. J.
Nakamura, Yusuke
Hamamoto, Ryuji
author_sort Hayami, Shinya
title Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway
title_short Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway
title_full Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway
title_fullStr Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway
title_full_unstemmed Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway
title_sort overexpression of the jmjc histone demethylase kdm5b in human carcinogenesis: involvement in the proliferation of cancer cells through the e2f/rb pathway
publisher BioMed Central
publishDate 2010
url http://psasir.upm.edu.my/id/eprint/40048/1/Overexpression%20of%20the%20JmjC%20histone.pdf
http://psasir.upm.edu.my/id/eprint/40048/
http://www.molecular-cancer.com/content/9/1/59/abstract
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score 13.211869

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