Muthusamy Ganesan, Liu Chin-Chi, Johnston Andrea N
Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA.
Cancers (Basel). 2023 Sep 29;15(19):4796. doi: 10.3390/cancers15194796.
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 Huh7 knockout 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, knockout 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，PGAM5的沉默会降低肿瘤生长，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的促肿瘤生存作用与脂质代谢相关。我们试图确定PGAM5的缺失是否会调节肝细胞癌中的脂滴积累。使用CRISPR/Cas9技术生成的HepG2和Huh7基因敲除细胞系用于测量细胞生长、细胞ATP和长链脂肪酸摄取。通过定量PCR和蛋白质免疫印迹法检测肝细胞脂肪酸转运蛋白、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）和脂肪酸结合蛋白1（FABP1）的表达。我们发现PGAM5的缺失会减弱肝癌细胞的生长和ATP生成。此外，基因敲除改善了棕榈酸诱导的脂肪变性，并降低了HepG2和Huh7细胞系中FABP1的表达。PGAM5在肝细胞癌中的作用包括调节脂肪酸代谢，这可能与脂肪酸转运蛋白FABP1的表达有关。
