KDM4C promotes prostate cancer metastasis via modulation of c-Myc and metabolic enzymes

[[abstract]]Prostate cancer (PCa) is the 5th most common cancer overall in the world. Recent studies suggest that metabolic reprograming in cancer is connected to changes at the epigenetic level. Our study focusing on investigating the role of histone lysine demethylases 4C (KDM4C) in PCa. The mRNA and protein expression of KDM4C is higher in human PCa tissues as compared to normal. Cox Survival Analysis revealed that PCa patients with higher KDM4C expression correlates to poor outcome. Knockdown of KDM4C by siRNA in PCa cells reduced cell proliferation, soft agar colony formation, migration, and invasion. Micro-Western Array (MWA) analysis indicated that reduction of KDM4C protein caused down-regulation of proteins involved in cell cycle regulators, c-Myc and epithelial-mesenchymal transition (EMT). Chromatin-IP experiment result suggested that KDM4C directly binds to c-Myc promoter region and regulates c-Myc genes expression. KDM4C regulates metabolic reprograming of cancer through regulation of c-Myc. Our finding suggested that knockdown of KDM4C shifts glycolytic metabolism to mitochondrial oxidation in prostate cancer cells, which may contribute to the suppression of cancer metastasis