一、BAP1在肝細胞癌中的作用 二、HIOMT在肝細胞癌中的作用

1. BAP1 in Hepatocellular carcinoma 2.HIOMT in Hepatocellular carcinoma

陳玟秀(Chen Wen-Hsiu)

指導教授 ： 張孜菁

國立臺灣師範大學/理學院/生命科學系/碩士(2021年)

https://doi.org/10.6345/NTNU202100367

摘要

BRCA1相關蛋白-1（BAP1）是一種泛素化酶，屬於泛素蛋白羧基末端水解酶亞型家族的成員，已被確認為腫瘤抑制基因。BAP1基因的重要性最初是在侵襲性葡萄膜黑色素瘤腫瘤樣本中檢測到無活性的BAP1突變時確立的。對癌症患者基因缺失數據的分析表明，與BAP1缺乏症相關的綜合症也已擴大到乳腺癌，透明細胞腎癌，肺腺癌，肝內膽管癌和胃腺癌。最近的研究發現，種系等位基因或體細胞突變與這些惡性腫瘤的進展和不良預後正相關。
儘管臨床患者中有許多基因缺失的統計數據，但是BAP1突變或缺失在消化道相關癌症（例如肝癌）中的作用和發病機理還不是很清楚，需要闡明。在這項研究中，我們評估BAP1缺失與癌症進展之間的關係，並檢測其可能的信號傳導機制。首先，我們進行siRNA敲除，以使BAP1失活，並在正常細胞系中過表達BAP1。其次，在上述BAP1失活或過表達的條件下，我們用BrdU和MTT測定法分析癌細胞的生長和活性，通過Boyden Transwell測定法分析細胞的遷移和侵襲，並以西方墨點法分析上皮-間質轉化（EMT）的相關蛋白E鈣黏蛋白和波型蛋白。我們希望這項研究的結果可以提供對BAP1失活在癌症進展中的全面了解，在癌症精準醫療時代提供BAP1突變失活病人可能的治療標靶路徑。

關鍵字

BRCA1相關蛋白-1 ； 5-甲氧基色胺酸 ； 肝細胞癌 ； 基因缺失 ； 上皮-間質轉化

並列摘要

BRCA1-related protein-1 (BAP-1) is a deubiquitinating enzyme that is a member of the ubiquitin C-terminal hydrolase subfamily. Although there are clinical data on gene deletions or overexpression of BAP-1 in cancer patients, the role and pathogenic mechanism of BAP-1 in liver cancer are not very clear. Recently, some papers have reported that BAP-1 involved in ferroptosis and epithelial-mesenchymal transition to promote tumor progression and metastasis. In this research, we find that BAP-1 inactivation facilitates the growth and migration of cancer stem cells (CSC-HCC) in hepatocellular carcinoma (HCC). In order to identify the role of BAP-1 on cell growth, metabolism, and migration in CSC-HCC, we performed BAP-1 over-expression, knock-down, and mutation in CSC-HCC. Cell growth and migration were analyzed with BrdU and transwell assay respectively. Mitochondria functions were detected with membrane potential and TFAM expression. Over-expression and knock-down of BAP-1 were carried out in CSC-HCC. Cell migration and growth were increased in CSC-HCC with BAP-1 siRNA treatment and decreased in cells with BAP-1 over-expression. Mitochondria biosynthesis were decreased due to TFAM reduction in CSC-HCC with BAP-1 siRNA treatment. BAP-1 inactivation affects the progression of HCC by the increase of cancer stem cell growth and migration.

並列關鍵字

BAP-1 ； HIOMT ； Hepatocellular carcinoma ； Mutation ； Epithelial-mesenchymal transition

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