醯基輔酶A硫酯酶可以將醯基輔酶A水解成游離脂肪酸以及輔酶A。雖然在1952年時就已經知道醯基輔酶A硫酯酶的催化活性，但是對於ACOTs家族在細胞和生物中具有的生理功能並不清楚。目前人類部分已發現ACOTs家族有十個成員，包含ACOT1、ACOT2、ACOT4、ACOT6、ACOT7、ACOT8、ACOT9、ACOT11、ACOT12和ACOT13，其中ACOTs家族中的ACOT8是位在過氧小體這個單膜的胞器之中。過去有很多研究指出當位於過氧小體中的酵素功能出現異常的時候可能會造成許多疾病包含老化甚至是癌症。此外，有研究指出ACOT8的mRNA在卵巢癌的檢體中發現會大量表現。雖然如此，ACOTs在癌症中扮演的角色至今尚未釐清。在此研究中，我們想要去了解位於過氧小體的ACOT8是否在肝癌中扮演重要的角色。一開始我們由GEO資料庫找尋關於肝癌檢體的數據庫並且進行生物晶片數據的分析，結果發現在肝癌病人中的ACOT8的基因拷貝數以及mRNA表現量有異常增加的現象。接下來我們進一步想知道ACOT8在肝癌中所具有的功能，為此我們利用Huh-7肝癌細胞株建立了將內生性ACOT8抑制的轉染細胞株。我們的數據指出當ACOT8表現量減少時會顯著的抑制細胞的生長能力。然後我們更進一步發現當ACOT8表現量減少時會透過活化TGF-beta路徑來增加p15INK4b和p27KIP1的蛋白質表現量，並誘導細胞週期延遲。此外，我們想要知道為何ACOT8表現量下降時可以影響TGF-beta的表現。由過去研究發現活性氧化物 (ROS) 的增加會抑制TGF-beta的表現，我們也發現在ACOT8被抑制後活性氧化物含量高的細胞比例會減少。

Acyl-Coenzyme A thioesterases (ACOTs) hydrolyze acyl-CoA esters to the free fatty acids (FFAs) and coenzyme A (CoASH). Although the catalytic activity of ACOTs was first identified in 1952, the physiological functions of ACOTs are not completely understood. The human ACOTs family consists of ten members, including ACOT1, ACOT2, ACOT4, ACOT6, ACOT8, ACOT9, ACOT11, ACOT12 and ACOT13. Among the Family, ACOT8 are localized in peroxisomes, which are single-membrane lined organelles. Previous studies show that aberrant functions of peroxisomal enzymes may cause many diseases such as aging and cancer. Moreover, some papers indicated that the mRNA expression of ACOT8 is increased in ovarian cancer. Nevertheless, the role of ACOTs in cancer is unclear. In this study, we are interested in studying the role of peroxisomal ACOT8 in liver cancer. At first, we searched for datasets relevant to hepatocellular carcinoma (HCC) specimens from gene expression omnibus (GEO) database and analyzed the microarray data. As a result, the gene copy number and mRNA expression level of ACOT8 was increased in HCC specimens. To investigate what are the functions of ACOT8 in liver tumor progression, we established ACOT8 knockdown clones of Huh-7 cells. Our data show that downregulation of ACOT8 reduces cell proliferation. Then, we further identified that downregulation of ACOT8 may increase the protein expression of p15INK4b and p27KIP1 through TGF-beta pathway and induce the cell cycle delay. Furthermore, we want to know why downregulation of ACOT8 may affect the expression of TGF-beta. Previous studies show that upregulation of reactive oxygen species (ROS) inhibit the expression of TGF-beta. We found that the percentage of high ROS cells was decreased in ACOT8 knockdown clones.

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