Kanda Tatsuo, Jiang Xia, Nakamura Masato, Haga Yuki, Sasaki Reina, Wu Shuang, Nakamoto Shingo, Imazeki Fumio, Yokosuka Osamu
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Department of General Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050031, P.R. China.
Oncol Lett. 2017 Jun;13(6):4481-4486. doi: 10.3892/ol.2017.5973. Epub 2017 Apr 3.
Hepatocellular carcinoma (HCC) is a predominantly male disease in which the androgen receptor (AR) serves an important pathogenic role in hepatocarcinogenesis. Fatty acid metabolism also contributes to hepatocarcinogenesis and is associated with the prognosis of cancer. The present study aimed to investigate the effects of the AR on fatty acid metabolism-associated gene expression in human hepatoma cell lines. AR-expression plasmids or control plasmids were transiently transfected into the human HCC cell lines Huh7 and HepG2. After 48 h, cellular protein and RNA were extracted and the expression of AR was confirmed by western blotting. Complementary DNA was synthesized and subjected to a quantitative polymerase chain reaction-based array to examine the expression of 84 fatty acid metabolism-associated genes. Overexpression of AR significantly downregulated the expression of 11 fatty acid metabolism-associated genes in Huh7 cells and 35 in HepG2 cells. The overexpression of AR also resulted in the upregulation of 6 fatty acid metabolism genes in HepG2 cells; however, it had no effect in Huh7 cells. Acyl-coenzyme A (CoA) thioesterase 7 and acyl-CoA oxidase 3 were downregulated in both cell lines. In conclusion, upregulation of AR via overexpression led to the disturbance of fatty acid metabolism-associated gene expression in human HCC cells. Therefore, the AR may serve a role in hepatocarcinogenesis via the regulation of hepatocellular fatty acid metabolism.
肝细胞癌(HCC)主要是一种男性疾病,其中雄激素受体(AR)在肝癌发生过程中起重要的致病作用。脂肪酸代谢也参与肝癌发生,并与癌症预后相关。本研究旨在探讨AR对人肝癌细胞系中脂肪酸代谢相关基因表达的影响。将AR表达质粒或对照质粒瞬时转染到人肝癌细胞系Huh7和HepG2中。48小时后,提取细胞蛋白和RNA,通过蛋白质印迹法确认AR的表达。合成互补DNA并进行基于定量聚合酶链反应的芯片分析,以检测84个脂肪酸代谢相关基因的表达。AR的过表达显著下调了Huh7细胞中11个脂肪酸代谢相关基因的表达以及HepG2细胞中35个相关基因的表达。AR的过表达还导致HepG2细胞中6个脂肪酸代谢基因上调;然而,在Huh7细胞中没有影响。两种细胞系中的酰基辅酶A(CoA)硫酯酶7和酰基辅酶A氧化酶3均下调。总之,通过过表达上调AR会导致人肝癌细胞中脂肪酸代谢相关基因表达紊乱。因此,AR可能通过调节肝细胞脂肪酸代谢在肝癌发生中发挥作用。