異常表觀遺傳的組蛋白修飾常伴隨著癌症的進展，KDM4C具有特異的催化活性能將組蛋白H3上的Lysine 9 與Lysine 36 的tri-methylation轉化為di-methylation。先前的研究已經闡述了KDM4C在復發的CRPC前列腺癌中表現較高。然而在前列腺癌細胞轉移與代謝中，KDM4C的角色仍然是未知的。在這項研究中，我們使用CRISPR技術將KDM4C在前列腺癌細胞中進行剔除。我們使用西方墨點微陣列平台來分析受到CRISPR剔除KDM4C的前列腺癌細胞其影響的下游信號傳導途徑。透過西方墨點微陣列揭示在剔除KDM4C後減少了葡萄糖代謝、線粒體代謝、能量代謝、PI3K / AKT信號通路與上皮間質轉化(EMT)中的許多蛋白質表現。我們觀察到剔除KDM4C抑制了前列腺癌細胞的遷移和侵襲能力，也降低了Snail, β-catenin, phospho-β-Catenin (Ser675), and PKA C-α, E-cadherin 的蛋白質表現。 我們使用Seahorse Bioscience XF分析儀證實剔除KDM4C後減少了前列腺癌細胞中的糖酵解、粒線體的基礎呼吸、ATP產量與粒線體的最大呼吸能力。在剔除KDM4C後，c-Myc, PKM2, LDHA, PDH, and PGC-1α的蛋白質表現也都是下降的。我們透過KDM4C會結合在c-Myc的啟動子區域發現KDM4C會直接調控c-Myc的基因轉錄。剔除KDM4C後發現乳酸分泌較低以及MMP2的活性降低。我們的結果表明在前列腺癌細胞中剔除KDM4C可能透過減少EMT、MMPs的活性、c-Myc以及干擾代謝減少癌細胞轉移。KDM4C是前列腺癌新的致癌基因，也具有潛力作為PCa的治療標的。

KDM4C, a member of lysine demethylase KDM4, converts tri-methylation to di-methylation of histone H3 at Lysine 9 (H3K9) and H3K36. Previous studies indicated that KDM4C expression level is higher in castration-resistant prostate cancer (CRPC). However, the role of KDM4C in prostate cancer (PCa) metastasis and metabolism is not well understood. In this study, we used Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to knockout KDM4C in C4-2B PCa cells. Micro-Western Array (MWA) platform was used to determine signaling proteins affected by CRISPR knockout of KDM4C in C4-2B cells. MWA revealed that knockout of KDM4C reduced proteins regulating glucose metabolism, mitochondrial metabolism, energy metabolism, PI3K/AKT signal pathway, and epithelial-mesenchymal transition (EMT). We observed that knockout of KDM4C suppressed the migration and invasion of C4-2B cells, as well as decreased the protein expression of Snail, β-catenin, phospho-β-Catenin (Ser675), PKA C-α, and E-cadherin. Seahorse Bioscience XF Analyzer analysis revealed that knockout of KDM4C reduces the glycolysis, basal respiration, ATP production, and maximum respiration of mitochondria in C4-2B cells. The protein expression of c-Myc, PKM2, LDHA, PDH, and PGC-1α, was downregulated in KDM4C knockout C4-2B cells. We discovered that KDM4C directly regulates c-Myc transcription by binding on the promoter region of c-Myc as determined by chromosome-IP (CHIP) assay. Knockout of KDM4C decreased lactate secretion and MMP2 activity. Our result suggested that knockout of KDM4C suppresses PCa metastasis possibly through inhibition of EMT marker, decrease of MMPs activity, reduction of c-Myc, and disturbing metabolism in PCa cells. KDM4C is thus a novel oncogene and a potential therapeutic target for PCa.

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