The Prognostic Significance of Histone Lysine Demethylase JMJD3/KDM6B in Colorectal Cancer

Ryuma Tokunaga, Yasuo Sakamoto, Shigeki Nakagawa, Keisuke Miyake, Daisuke Izumi, Keisuke Kosumi, Katsunobu Taki, Takaaki Higashi, Yu Imamura, Takatsugu Ishimoto, Masaaki Iwatsuki, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Eiji Oki, Masayuki Watanabe, Hideo Baba

Research output: Contribution to journalArticle

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Abstract

Background: Jumonji-domain containing 3 (JMJD3) affects transcriptional regulation by demethylating lysine 27 residue of histone 3. We investigated its function and prognostic significance in colorectal cancer (CRC). Methods: The influence of JMJD3 on cell proliferation was assessed using quantitative RT-PCR and western blot on the downstream target gene of JMJD3, in knock-down (KD) experiments and clinical samples from 151 CRC patients. Results: Cells with KD JMJD3 significantly increased proliferation through cell cycle progression and apoptosis suppression. Expression of P15INK4B was remarkably decreased in KD JMJD3 cells; and JMJD3 expression strongly correlated with p15INK4B expression in clinical CRC samples (P < 0.001, r = 0.566). Low JMJD3 also was an independent predictor of poor prognosis (P = 0.042) in surgically resected CRC patients. Conclusions: JMJD3 has prognostic significance in CRC and mediates p15INK4B expression. These results imply that elucidation of the JMJD3 role may lead to a new therapeutic approach for CRC patients.

Original languageEnglish
Pages (from-to)678-685
Number of pages8
JournalAnnals of Surgical Oncology
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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Histone Demethylases
Colorectal Neoplasms
Histones
Lysine
Cell Cycle
Western Blotting
Cell Proliferation
Apoptosis
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Tokunaga, R., Sakamoto, Y., Nakagawa, S., Miyake, K., Izumi, D., Kosumi, K., ... Baba, H. (2016). The Prognostic Significance of Histone Lysine Demethylase JMJD3/KDM6B in Colorectal Cancer. Annals of Surgical Oncology, 23(2), 678-685. https://doi.org/10.1245/s10434-015-4879-3

The Prognostic Significance of Histone Lysine Demethylase JMJD3/KDM6B in Colorectal Cancer. / Tokunaga, Ryuma; Sakamoto, Yasuo; Nakagawa, Shigeki; Miyake, Keisuke; Izumi, Daisuke; Kosumi, Keisuke; Taki, Katsunobu; Higashi, Takaaki; Imamura, Yu; Ishimoto, Takatsugu; Iwatsuki, Masaaki; Baba, Yoshifumi; Miyamoto, Yuji; Yoshida, Naoya; Oki, Eiji; Watanabe, Masayuki; Baba, Hideo.

In: Annals of Surgical Oncology, Vol. 23, No. 2, 01.02.2016, p. 678-685.

Research output: Contribution to journalArticle

Tokunaga, R, Sakamoto, Y, Nakagawa, S, Miyake, K, Izumi, D, Kosumi, K, Taki, K, Higashi, T, Imamura, Y, Ishimoto, T, Iwatsuki, M, Baba, Y, Miyamoto, Y, Yoshida, N, Oki, E, Watanabe, M & Baba, H 2016, 'The Prognostic Significance of Histone Lysine Demethylase JMJD3/KDM6B in Colorectal Cancer', Annals of Surgical Oncology, vol. 23, no. 2, pp. 678-685. https://doi.org/10.1245/s10434-015-4879-3
Tokunaga, Ryuma ; Sakamoto, Yasuo ; Nakagawa, Shigeki ; Miyake, Keisuke ; Izumi, Daisuke ; Kosumi, Keisuke ; Taki, Katsunobu ; Higashi, Takaaki ; Imamura, Yu ; Ishimoto, Takatsugu ; Iwatsuki, Masaaki ; Baba, Yoshifumi ; Miyamoto, Yuji ; Yoshida, Naoya ; Oki, Eiji ; Watanabe, Masayuki ; Baba, Hideo. / The Prognostic Significance of Histone Lysine Demethylase JMJD3/KDM6B in Colorectal Cancer. In: Annals of Surgical Oncology. 2016 ; Vol. 23, No. 2. pp. 678-685.
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AU - Nakagawa, Shigeki

AU - Miyake, Keisuke

AU - Izumi, Daisuke

AU - Kosumi, Keisuke

AU - Taki, Katsunobu

AU - Higashi, Takaaki

AU - Imamura, Yu

AU - Ishimoto, Takatsugu

AU - Iwatsuki, Masaaki

AU - Baba, Yoshifumi

AU - Miyamoto, Yuji

AU - Yoshida, Naoya

AU - Oki, Eiji

AU - Watanabe, Masayuki

AU - Baba, Hideo

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N2 - Background: Jumonji-domain containing 3 (JMJD3) affects transcriptional regulation by demethylating lysine 27 residue of histone 3. We investigated its function and prognostic significance in colorectal cancer (CRC). Methods: The influence of JMJD3 on cell proliferation was assessed using quantitative RT-PCR and western blot on the downstream target gene of JMJD3, in knock-down (KD) experiments and clinical samples from 151 CRC patients. Results: Cells with KD JMJD3 significantly increased proliferation through cell cycle progression and apoptosis suppression. Expression of P15INK4B was remarkably decreased in KD JMJD3 cells; and JMJD3 expression strongly correlated with p15INK4B expression in clinical CRC samples (P < 0.001, r = 0.566). Low JMJD3 also was an independent predictor of poor prognosis (P = 0.042) in surgically resected CRC patients. Conclusions: JMJD3 has prognostic significance in CRC and mediates p15INK4B expression. These results imply that elucidation of the JMJD3 role may lead to a new therapeutic approach for CRC patients.

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