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Annals of Surgical Oncology

, Volume 23, Issue 2, pp 678–685 | Cite as

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 BabaEmail author
Translational Research and Biomarkers

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.

Keywords

Overall Survival Suppress Apoptosis Normal Colorectal Epithelial Tissue JMJD3 Expression p16INK4A mRNA 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

The authors thank Naomi Yokoyama, Yoko Ogata, and Hiroko Taniguchi for their valuable technical assistance.

Disclosure

The authors have no conflict of interest to declare.

Supplementary material

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Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Ryuma Tokunaga
    • 1
  • Yasuo Sakamoto
    • 1
  • Shigeki Nakagawa
    • 1
  • Keisuke Miyake
    • 1
  • Daisuke Izumi
    • 1
  • Keisuke Kosumi
    • 1
  • Katsunobu Taki
    • 1
  • Takaaki Higashi
    • 1
  • Yu Imamura
    • 1
  • Takatsugu Ishimoto
    • 1
  • Masaaki Iwatsuki
    • 1
  • Yoshifumi Baba
    • 1
  • Yuji Miyamoto
    • 1
  • Naoya Yoshida
    • 1
  • Eiji Oki
    • 2
  • Masayuki Watanabe
    • 3
  • Hideo Baba
    • 1
    Email author
  1. 1.Department of Gastroenterological Surgery, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
  2. 2.Department of Surgery and Sciences, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Gastroenterological SurgeryJapanese Foundation for Cancer ResearchTokyoJapan

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