Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular Carcinoma
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, wh...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/19/4796 |
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| author | Ganesan Muthusamy Chin-Chi Liu Andrea N. Johnston |
| author_facet | Ganesan Muthusamy Chin-Chi Liu Andrea N. Johnston |
| author_sort | Ganesan Muthusamy |
| collection | DOAJ |
| description | 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 <i>PGAM5</i> 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, <i>PGAM5</i> 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. |
| first_indexed | 2024-03-10T21:47:27Z |
| format | Article |
| id | doaj.art-3fa13462df3445e2b68011df11ef5d0e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:47:27Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3fa13462df3445e2b68011df11ef5d0e2023-11-19T14:10:41ZengMDPI AGCancers2072-66942023-09-011519479610.3390/cancers15194796Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular CarcinomaGanesan Muthusamy0Chin-Chi Liu1Andrea N. Johnston2Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USALouisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USALouisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USAPhosphoglycerate 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 <i>PGAM5</i> 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, <i>PGAM5</i> 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.https://www.mdpi.com/2072-6694/15/19/4796liver cancerlong-chain fatty acidsfatty acid transporters |
| spellingShingle | Ganesan Muthusamy Chin-Chi Liu Andrea N. Johnston Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular Carcinoma Cancers liver cancer long-chain fatty acids fatty acid transporters |
| title | Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular Carcinoma |
| title_full | Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular Carcinoma |
| title_fullStr | Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular Carcinoma |
| title_full_unstemmed | Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular Carcinoma |
| title_short | Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular Carcinoma |
| title_sort | deletion of pgam5 downregulates fabp1 and attenuates long chain fatty acid uptake in hepatocellular carcinoma |
| topic | liver cancer long-chain fatty acids fatty acid transporters |
| url | https://www.mdpi.com/2072-6694/15/19/4796 |
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