循環農業：農業廢棄物再資源化—研發低碳農業技術【食品暨應用生物科技學系/蔣恩沛教授】
| 論文篇名 | 英文：Translocation of Methionine Adenosyl Transferase MAT2A and Its Prognostic Relevance for Liver Hepatocellular Carcinoma 中文：甲硫胺酸胺核苷轉移酶 MAT2A 的易位與其對肝臟肝細胞癌的預後相關性 |
| 期刊名稱 | International Journal of Molecular Sciences |
| 發表年份,卷數,起迄頁數 | 2023, 24 (10): 9103 |
| 作者 | Chu, Pei-Yi; Chou, Dev-Aur; Chen, Po-Ming; Chiang, En-Pei Isabel(蔣恩沛)* |
| DOI | 10.3390/ijms24109103 |
| 中文摘要 | 甲硫胺酸胺核苷轉移酶MAT1A催化生物甲基提供者腺苷甲硫胺酸的合成。此酶的失調與人類致癌過程有關。我們之前發現 MAT1A 基因的下調會提高蛋白質相關的轉譯過程，並加劇肝臟肝癌預後之惡化。我們還發現 MAT2A 蛋白於細胞體內的位置與乳腺癌患者的獨立預後相關。本研究旨在探討 MAT2A 易位在人類肝癌之臨床相關性。我們使用基因表達譜數據動態分析 2 (GEPIA2) 分析 TCGA LIHC 數據中必需甲硫胺酸循環的基因表現, 並以免疫組織化學法，在 LIHC 群體 (n = 261) 的組織切片中偵測 MAT2A 蛋白之表達分佈，並以 Kaplan-Meier 生存曲線探討 MAT2A 蛋白於細胞分佈與預後之相關性。LIHC 患者的 MAT2A mRNA 表現越高，存活率越差 (p = 0.0083)。組織切片中細胞質與細胞核兩個部分均有觀察到 MAT2A 蛋白的免疫反應活性。腫瘤組織內細胞質與細胞核中 MAT2A 蛋白的表現均高於其相鄰的正常組織。女性 LIHC 患者的細胞質/細胞核 MAT2A 蛋白表現比 (C/N) 高於男性患者 (p = 0.047)。Kaplan-Meier 生存曲線顯示，女性 LIHC 患者中較低的 MAT2A C/N 與較差的總體存活有相關性 (10 年存活率：29.2% vs. 68.8%，C/N ≤ 1.0 vs. C/N > 1.0，對數等級 p = 0.004)。此外，我們檢視蛋白質-蛋白質交互作用預估，通過 GeneMANIA 計算發現，特異性蛋白 1 (SP1) 可能與核內 MAT2A 蛋白有潛在交互作用。我們通過人類蛋白質地圖 (HPA) 探索雌激素軸在 LIHC 中的潛在保護作用，發現支持雌激素相關蛋白 ESSRG 在 LIHC 中可能具有保護作用之證據。SP1 與 MAT2 的定位可能與 LIHC 中 ESRRG 之表現呈負相關。本研究闡明 MAT2A 的易位與其在女性 LIHC 患者中的預後相關性。本研究結果顯示雌激素在 SP1 調節與 MAT2A 的定位對 LIHC 女性患者可能具有治療的潛力。 |
| 英文摘要 | Methionine adenosyl transferases (MATs) catalyze the synthesis of the biological methyl donor adenosylmethionine (SAM). Dysregulation of MATs has been associated with carcinogenesis in humans. We previously found that downregulation of the MAT1A gene enriches the protein-associated translation process and worsens liver hepatocellular carcinoma (LIHC) prognosis. We also discovered that subcellular localization of the MAT2A protein has independently prognostic relevance in breast cancer patients. The present study aimed to examined the clinical relevance of MAT2A translocation in human LIHC. Essential methionine cycle gene expressions in TCGA LIHC datasets were analyzed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2). The protein expression pattern of MAT2A was determined in the tissue array of our own LIHC cohort (n = 261) using immuno-histochemistry, and the prognostic relevance of MAT2A protein's subcellular localization expression was examined using Kaplan-Meier survival curves. LIHC patients with higher MAT2A mRNA expression had a worse survival rate (p = 0.0083). MAT2A protein immunoreactivity was observed in both cytoplasm and nucleus fractions in the tissue array. Tumor tissues had elevated MAT2A protein expression in both cytoplasm and nucleus compared to their adjacent normal tissues. A higher cytoplasmic to nuclear MAT2A protein expression ratio (C/N) was found in female LIHC patients compared to that of male patients (p = 0.047). Kaplan-Meier survival curves showed that a lower MAT2A C/N correlated with poor overall survival in female LIHC patients (10-year survival rate: 29.2% vs. 68.8%, C/N ≤ 1.0 vs. C/N > 1.0, log-rank p = 0.004). Moreover, we found that specificity protein 1 (SP1) may have a potential interaction with nuclear MAT2A protein, using protein-protein interaction; this we found using the GeneMANIA algorithm. We explored the possible protective effects of the estrogen axis in LIHC using the Human Protein Atlas (HPA), and found evidence supporting a possible protective effect of estrogen-related protein ESSRG in LIHC. The localization of SP1 and MAT2 appeared to be inversely associated with ESRRG expression in LIHC. The present study demonstrated the translocation of MAT2A and its prognostic relevance in female LIHC patients. Our findings suggest the potential of estrogen in SP1 regulation and localization of MAT2A, as therapeutic modalities against in female LIHC patients. |
| 發表成果與本中心研究主題相關性 | 代謝路徑分析及資訊數據庫之分析與應用 |
