Huang Li, Li Lixing, Cheng Bin, Xing Tonghai
Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of General Surgery, Shanghai Xuhui District Central Hospital, Shanghai, China.
Carcinogenesis. 2022 Oct 22;43(9):885-894. doi: 10.1093/carcin/bgac061.
Hepatocellular carcinoma (HCC) is a common form of liver cancer. The incidence of HCC is increasing and effective prevention methods are needed. The solute carrier family 38 member 6 (SLC38A6) plays an important role in the metabolism of glutamine, which is a central nutrient for many cancers. However, the regulation and function of SLC38A6 in HCC are unclear. SLC38A6 levels in human HCC tissue arrays and cells were determined. SLC38A6 was silenced or overexpressed to determine its role in regulating cell viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration. A luminescence assay was used to study the interaction between SLC38A6 and EP300. The interactions between SLC38A6, H3K27ac and EP300 were determined using chromatin immunoprecipitation assays. Quantitative RT-PCR and immunoblots were performed to measure mRNAs and proteins, respectively. SLC38A6 expression was higher in HCC compared with expression in normal tissue. Silencing SLC38A6 inhibited cell viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration, while SLC38A6 overexpression had the opposite effects. Silencing SLC38A6 also inhibited tumor growth in vivo. Silencing EP300 significantly suppressed the interaction between H3K27ac and the SLC38A6 promoter, leading to decreased SLC38A6. SLC38A6 is regulated by EP300-mediated modifications of H3K27ac and promotes viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration in HCC cells.
肝细胞癌（HCC）是肝癌的一种常见形式。HCC的发病率正在上升，因此需要有效的预防方法。溶质载体家族38成员6（SLC38A6）在谷氨酰胺代谢中起重要作用，谷氨酰胺是许多癌症的核心营养物质。然而，SLC38A6在HCC中的调控和功能尚不清楚。研究人员测定了人HCC组织芯片和细胞中SLC38A6的水平。通过使SLC38A6沉默或过表达来确定其在调节细胞活力、集落形成、细胞周期进程、谷氨酰胺代谢和线粒体呼吸中的作用。采用发光分析法研究SLC38A6与EP300之间的相互作用。利用染色质免疫沉淀分析法确定SLC38A6、H3K27ac和EP300之间的相互作用。分别进行定量RT-PCR和免疫印迹法来检测mRNA和蛋白质。与正常组织中的表达相比，HCC中SLC38A6的表达更高。沉默SLC38A6可抑制细胞活力、集落形成、细胞周期进程、谷氨酰胺代谢和线粒体呼吸，而SLC38A6过表达则产生相反的效果。沉默SLC38A6也会抑制体内肿瘤生长。沉默EP300可显著抑制H3K27ac与SLC38A6启动子之间的相互作用，导致SLC38A6减少。SLC38A6受EP300介导的H3K27ac修饰调控，并促进HCC细胞的活力、集落形成、细胞周期进程、谷氨酰胺代谢和线粒体呼吸。
