The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G 1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene

Hyun Soo Cho, Gouji Toyokawa, Yataro Daigo, Shinya Hayami, Ken Masuda, Noriko Ikawa, Yuka Yamane, Kazuhiro Maejima, Tatsuhiko Tsunoda, Helen I. Field, John D. Kelly, David E. Neal, Bruce A.J. Ponder, Yoshihiko Maehara, Yusuke Nakamura, Ryuji Hamamoto

Research output: Contribution to journalArticle

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Abstract

A number of histone demethylases have been identified and biochemically characterized, yet their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. In this study, we describe important roles for the histone demethylase KDM3A, also known as JMJD1A, in human carcinogensis. Expression levels of KDM3A were significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (p < 0.0001), when assessed by real-time PCR. We confirmed that some other cancers including lung cancer also overexpressed KDM3A, using cDNA microarray analysis. Treatment of cancer cell lines with small interfering RNA targeting KDM3A significantly knocked down its expression and resulted in the suppression of proliferation. Importantly, we found that KDM3A activates transcription of the HOXA1 gene through demethylating histone H3 at lysine 9 di-methylation by binding to its promoter region. Indeed, expression levels of KDM3A and HOXA1 in several types of cancer cell lines and bladder cancer samples were statistically correlated. We observed the down-regulation of HOXA1 as well as CCND1 after treatment with KDM3A siRNA, indicating G 1 arrest of cancer cells. Together, our results suggest that elevated expression of KDM3A plays a critical role in the growth of cancer cells, and further studies may reveal a cancer therapeutic potential in KDM3A inhibition.

Original languageEnglish
Pages (from-to)E179-E189
JournalInternational Journal of Cancer
Volume131
Issue number3
DOIs
Publication statusPublished - Aug 1 2012

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Jumonji Domain-Containing Histone Demethylases
Histone Demethylases
Genes
Neoplasms
Small Interfering RNA
Lung Neoplasms
Urinary Bladder
Cell Line
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Genetic Promoter Regions
Urinary Bladder Neoplasms
Histones
Methylation
Lysine
Real-Time Polymerase Chain Reaction
Down-Regulation
Carcinoma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G 1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene. / Cho, Hyun Soo; Toyokawa, Gouji; Daigo, Yataro; Hayami, Shinya; Masuda, Ken; Ikawa, Noriko; Yamane, Yuka; Maejima, Kazuhiro; Tsunoda, Tatsuhiko; Field, Helen I.; Kelly, John D.; Neal, David E.; Ponder, Bruce A.J.; Maehara, Yoshihiko; Nakamura, Yusuke; Hamamoto, Ryuji.

In: International Journal of Cancer, Vol. 131, No. 3, 01.08.2012, p. E179-E189.

Research output: Contribution to journalArticle

Cho, HS, Toyokawa, G, Daigo, Y, Hayami, S, Masuda, K, Ikawa, N, Yamane, Y, Maejima, K, Tsunoda, T, Field, HI, Kelly, JD, Neal, DE, Ponder, BAJ, Maehara, Y, Nakamura, Y & Hamamoto, R 2012, 'The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G 1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene', International Journal of Cancer, vol. 131, no. 3, pp. E179-E189. https://doi.org/10.1002/ijc.26501
Cho, Hyun Soo ; Toyokawa, Gouji ; Daigo, Yataro ; Hayami, Shinya ; Masuda, Ken ; Ikawa, Noriko ; Yamane, Yuka ; Maejima, Kazuhiro ; Tsunoda, Tatsuhiko ; Field, Helen I. ; Kelly, John D. ; Neal, David E. ; Ponder, Bruce A.J. ; Maehara, Yoshihiko ; Nakamura, Yusuke ; Hamamoto, Ryuji. / The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G 1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene. In: International Journal of Cancer. 2012 ; Vol. 131, No. 3. pp. E179-E189.
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AU - Daigo, Yataro

AU - Hayami, Shinya

AU - Masuda, Ken

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AU - Field, Helen I.

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AU - Neal, David E.

AU - Ponder, Bruce A.J.

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