The prognostic significance of histone lysine demethylase JMJD3/KDM6B in colorectal cancer

R Tokunaga, Y Sakamoto, S Nakagawa… - Annals of surgical …, 2016 - Springer
R Tokunaga, Y Sakamoto, S Nakagawa, K Miyake, D Izumi, K Kosumi, K Taki, T Higashi…
Annals of surgical oncology, 2016Springer
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 …
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.
Springer