酰基辅酶A硫酯酶7被Krüppel样因子13转录激活并促进肝细胞癌进展。
Acyl-CoA Thioesterase 7 is Transcriptionally Activated by Krüppel-Like Factor 13 and Promotes the Progression of Hepatocellular Carcinoma.
作者信息
Xie Xingming, Chen Chaochun, Feng Shu, Zuo Shi, Zhao Xueke, Li Haiyang
机构信息
School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
出版信息
J Hepatocell Carcinoma. 2021 Dec 23;8:1623-1641. doi: 10.2147/JHC.S338353. eCollection 2021.
PURPOSE
Acyl-CoA thioesterase 7(ACOT7) plays an important role in the metabolism of fatty acids. Hepatocellular carcinoma (HCC) has an abnormal lipid profile, and the role of ACOT7 in hepatocellular carcinoma has not been detailedly elucidated. Therefore, we conducted the study to explore the role of ACOT7 in HCC.
MATERIALS AND METHODS
The ACOT7 and Krüppel-like factor 13 (KLF13) mRNA expression levels were obtained from The Cancer Genome Atlas (TCGA) database. Bioinformatics analysis identified the underlying upstream regulator of ACOT7. Quantitative real-time PCR was used to detect the expression of mRNA, and immunohistochemical staining and Western blotting were used to detect the expression of protein. Cell Counting Kit-8 and EdU assays were employed to assess the proliferation of HCC cells. Wound-healing and Transwell migration assays were utilized to test the migration ability of HCC cells. Dual-luciferase reporter assay and ChIP assay were used to explore the potential mechanism. Gas chromatography-mass spectrometer was used to analyze the content of free fatty acids. Xenograft tumour growth was used to evaluate the effect of ACOT7 in vivo.
RESULTS
According to The Cancer Genome Atlas (TCGA) database, ACOT7 mRNA was found to be upregulated and predicted the poor prognosis. Overexpression of ACOT7 enhanced the proliferation, migration and invasion abilities of HCC cells in vitro, as well as the HCC cells proliferation in vivo. Moreover, ACOT7 overexpression increased the yield of the monounsaturated fatty acid Oleic acid (C18:1), which strengthened the proliferation and migration abilities of HCC cells. Mechanistically, KLF13 transcriptionally promoted ACOT7 expression. Further, KLF13 was also overexpressed in HCC tissues and facilitated HCC progression.
CONCLUSION
Acyl-CoA thioesterase 7 is transcriptionally activated by Krüppel-like factor 13 and promotes the progression of hepatocellular carcinoma.
目的
酰基辅酶A硫酯酶7（ACOT7）在脂肪酸代谢中起重要作用。肝细胞癌（HCC）存在脂质谱异常，而ACOT7在肝细胞癌中的作用尚未得到详细阐明。因此，我们开展本研究以探讨ACOT7在HCC中的作用。
材料与方法
从癌症基因组图谱（TCGA）数据库获取ACOT7和Krüppel样因子13（KLF13）的mRNA表达水平。生物信息学分析确定了ACOT7潜在的上游调节因子。采用定量实时PCR检测mRNA表达，免疫组织化学染色和蛋白质印迹法检测蛋白质表达。使用细胞计数试剂盒-8和EdU检测评估HCC细胞的增殖。采用伤口愈合实验和Transwell迁移实验检测HCC细胞的迁移能力。利用双荧光素酶报告基因实验和染色质免疫沉淀实验探索潜在机制。采用气相色谱-质谱联用仪分析游离脂肪酸含量。通过异种移植瘤生长评估ACOT7在体内的作用。
结果
根据癌症基因组图谱（TCGA）数据库，发现ACOT7 mRNA上调并预测预后不良。ACOT7过表达增强了体外HCC细胞的增殖、迁移和侵袭能力，以及体内HCC细胞的增殖能力。此外，ACOT7过表达增加了单不饱和脂肪酸油酸（C18:1）的产量，增强了HCC细胞的增殖和迁移能力。机制上，KLF13转录促进ACOT7表达。此外，KLF13在HCC组织中也过表达并促进HCC进展。
结论
酰基辅酶A硫酯酶7被Krüppel样因子13转录激活并促进肝细胞癌进展。
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