Journal of Hepatocellular Carcinoma (Dec 2021)
Acyl-CoA Thioesterase 7 is Transcriptionally Activated by Krüppel-Like Factor 13 and Promotes the Progression of Hepatocellular Carcinoma
Abstract
Xingming Xie,1,2 Chaochun Chen,1,2 Shu Feng,1,3 Shi Zuo,2 Xueke Zhao,3 Haiyang Li1,2 1School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Haiyang LiDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, Guizhou, People’s Republic of ChinaTel/Fax +86 851-6855119Email [email protected]: 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.Keywords: acyl-CoA thioesterase 7, Krüppel-like factor 13, hepatocellular carcinoma, unsaturated fatty acid, prognosis
