Phosphoglycerate mutase 5 (PGAM5) is a Ser/His/Thr phosphatase responsible for regulating mitochondrial homeostasis. Overexpression of PGAM5 is correlated with a poor prognosis in hepatocellular carcinoma, colon cancer, and melanoma. In hepatocellular carcinoma, silencing of PGAM5 reduces growth, which has been attributed to decreased mitophagy and enhanced apoptosis. Yet in colon cancer, PGAM5’s pro-tumor survival effect is correlated to lipid metabolism. We sought to identify whether deletion of PGAM5 modulated lipid droplet accrual in hepatocellular carcinoma. HepG2 and Huh7PGAM5knockout cell lines generated using CRISPR/Cas9 technology were used to measure cell growth, cellular ATP, and long-chain fatty acid uptake. Expression of hepatocellular fatty acid transporters, cluster of differentiation 36 (CD36), solute carrier family 27 member 2 (SLC27A2), solute carrier family 27 member 5 (SLC27A5), and fatty acid binding protein 1 (FABP1) was measured by quantitative PCR and Western blot. We found that deletion of PGAM5 attenuates hepatocellular carcinoma cell growth and ATP production. Further,PGAM5knockout ameliorates palmitate-induced steatosis and reduces expression of FABP1 in HepG2 and Huh7 cell lines. PGAM5’s role in hepatocellular carcinoma includes regulation of fatty acid metabolism, which may be related to expression of the fatty acid transporter, FABP1.
磷酸甘油酸变位酶5（PGAM5）是一种丝氨酸/组氨酸/苏氨酸磷酸酶，负责调节线粒体稳态。PGAM5的过表达与肝细胞癌、结肠癌和黑色素瘤的不良预后相关。在肝细胞癌中，沉默PGAM5可抑制肿瘤生长，这归因于线粒体自噬减少和细胞凋亡增强。然而在结肠癌中，PGAM5的促肿瘤生存效应与脂质代谢相关。本研究旨在探究PGAM5缺失是否调节肝细胞癌中的脂滴积累。通过CRISPR/Cas9技术构建的HepG2和Huh7 PGAM5敲除细胞系被用于检测细胞生长、细胞ATP水平及长链脂肪酸摄取。采用定量PCR和蛋白质印迹法检测肝细胞脂肪酸转运蛋白的表达水平，包括分化簇36（CD36）、溶质载体家族27成员2（SLC27A2）、溶质载体家族27成员5（SLC27A5）以及脂肪酸结合蛋白1（FABP1）。研究发现，PGAM5缺失可减弱肝细胞癌细胞的生长和ATP生成。此外，PGAM5敲除能改善棕榈酸酯诱导的脂肪变性，并降低HepG2和Huh7细胞系中FABP1的表达。PGAM5在肝细胞癌中的作用涉及脂肪酸代谢的调控，这可能与脂肪酸转运蛋白FABP1的表达相关。
肿瘤(癌症)患者之家