PMID- 26416711 OWN - NLM STAT- MEDLINE DCOM- 20161025 LR - 20220330 IS - 1534-4681 (Electronic) IS - 1068-9265 (Linking) VI - 23 IP - 2 DP - 2016 Feb TI - The Prognostic Significance of Histone Lysine Demethylase JMJD3/KDM6B in Colorectal Cancer. PG - 678-85 LID - 10.1245/s10434-015-4879-3 [doi] AB - 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. FAU - Tokunaga, Ryuma AU - Tokunaga R AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Sakamoto, Yasuo AU - Sakamoto Y AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Nakagawa, Shigeki AU - Nakagawa S AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Miyake, Keisuke AU - Miyake K AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Izumi, Daisuke AU - Izumi D AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Kosumi, Keisuke AU - Kosumi K AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Taki, Katsunobu AU - Taki K AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Higashi, Takaaki AU - Higashi T AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Imamura, Yu AU - Imamura Y AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Ishimoto, Takatsugu AU - Ishimoto T AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Iwatsuki, Masaaki AU - Iwatsuki M AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Baba, Yoshifumi AU - Baba Y AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Miyamoto, Yuji AU - Miyamoto Y AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Yoshida, Naoya AU - Yoshida N AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Oki, Eiji AU - Oki E AD - Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Watanabe, Masayuki AU - Watanabe M AD - Department of Gastroenterological Surgery, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Baba, Hideo AU - Baba H AD - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. hdobaba@kumamoto-u.ac.jp. LA - eng PT - Journal Article DEP - 20150928 PL - United States TA - Ann Surg Oncol JT - Annals of surgical oncology JID - 9420840 RN - 0 (Biomarkers, Tumor) RN - 0 (RNA, Messenger) RN - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases) RN - EC 1.14.11.- (KDM6B protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Apoptosis MH - Biomarkers, Tumor/genetics/*metabolism MH - Cell Cycle MH - Cell Proliferation MH - Colorectal Neoplasms/enzymology/genetics/*pathology MH - Female MH - Follow-Up Studies MH - Humans MH - Immunoenzyme Techniques MH - Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism MH - Male MH - Middle Aged MH - Neoplasm Invasiveness MH - Neoplasm Staging MH - Prognosis MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Retrospective Studies MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survival Rate MH - Tumor Cells, Cultured EDAT- 2015/09/30 06:00 MHDA- 2016/10/26 06:00 CRDT- 2015/09/30 06:00 PHST- 2015/01/14 00:00 [received] PHST- 2015/09/30 06:00 [entrez] PHST- 2015/09/30 06:00 [pubmed] PHST- 2016/10/26 06:00 [medline] AID - 10.1245/s10434-015-4879-3 [pii] AID - 10.1245/s10434-015-4879-3 [doi] PST - ppublish SO - Ann Surg Oncol. 2016 Feb;23(2):678-85. doi: 10.1245/s10434-015-4879-3. Epub 2015 Sep 28.