MicroRNA122對於肝細胞致癌現象的代謝通量分析

肝臟是人體最重要的代謝中心(人體的化工廠)，許多物質和營養素都是在肝這個代謝中心進行代謝作用、轉化作用、解毒功能、合成蛋白質、排泄功能，因此肝在我們人體中扮演很重要的角色。在正常細胞的代謝活化主要依賴於粒線體氧化磷酸化（Oxidative phosphorylation）生成的三磷酸腺苷(Adenosine triphosphate，ATP)來提供能量，但在細胞趨向癌化的狀態，糖酵解(glycolysis) 路徑效能會增強，且比較傾向走產生乳酸(lactate)的路徑，而比較不走進入檸檬酸循環(TCA cycle)的路徑，符合這種現象的狀態稱做沃伯格效應(Warburg Effect)。本研究利用肝細胞代謝網路模型Recon2 liver model，在三磷酸腺苷(Adenosine triphosphate，ATP)最大化且內部通量最小化狀態下，進行通量均衡分析方法(Flux balance analysis, FBA)的計算。接著以陽明大學鄒安平教授團隊提供的老鼠 miR-122a target genes對應到Recon 2 liver model 共有20個target genes所表現的酵素，進行模擬突變通量均衡分析方法(Mutant Flux balance analysis, mFBA)的計算。FBA得到的穩態通量分佈，在與mFBA的穩態通量分布結果做比對，結果發現調控這20個miR-122a target genes中，有一半以上的酵素模擬結果與Warburg Effect 及實驗數據現象類似率達到50%以上。且我們也發現調控Ddc酵素模擬結果與Warburg effect的類似率高達到95%，所以在肝細胞癌化中扮演很重要的角色。

關鍵字

Recon2 liver model ； Mir122a ；癌化；肝臟

並列摘要

The liver was the the most important metabolic center in the human body (or the chemical plant of human body). Many substances and nutrients were processed by transformation, detoxification, protein synthesis and excretion in liver. Therefore, the liver played a critical role in our body .Ordinary cells depend on the metabolic activation of mitochondrial oxidative phosphorylation generating ATP to provide energy. But when it tended to become cancerous cell, the flux of glycolysis enhances and the reaction prefered to produce lactate rather than to participate the series reaction of tricarboxylic acid cycle (TCA cycle). In this study, the metabolic network model of liver cells Recon2 liver model, the analysis method (Flux balance analysis, FBA) was calculated optimal flux balance. Then the tumor suppressor gene Mir122a shave target gene, the method for analysis (Mutant Flux balance analysis, mFBA) mutant analog flux balance calculation. Steady-state flux distribution obtained FBA, in steady-state flux distribution with mFBA results do compare .The results indicated that over a half of these miR-122a target genes had fifty percent similarity to the analysis experimental data of Warburg effect & LC-MS And we also found that Ddc enzyme similar with Warburg effect to up to 95%.In conclusion ,Ddc played a critical role in the liver cell.

並列關鍵字

Recon2 liver model ； carcinogenesis ； liver ； Mir122a

參考文獻

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MicroRNA122對於肝細胞致癌現象的代謝通量分析

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