Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

Abstract

Tyrosine is an essential ketogenic and glycogenic amino acid for the human body, which means that tyrosine is not only involved in protein metabolism, but also participates in the metabolism of lipids and carbohydrates. The liver is an important place for metabolism of lipids, carbohydrates, and proteins. The metabolic process of biological macro-molecules is a basis for maintaining the physiological activities of organisms, but the cross-linking mechanism of these processes is still unclear. Here, we found that the tyrosine-metabolizing enzymes, which were specifically and highly expressed in the liver, were significantly down-regulated in hepatocellular carcinoma (HCC), and had a correlation with a poor prognosis of HCC patients. Further analysis found that the reduction of tyrosine metabolism would activate the cell cycle and promote cell proliferation. In addition, we also found that the solute carrier family 27 member 5 (SLC27A5) regulates the expression of tyrosine-metabolizing enzymes through nuclear factor erythroid 2-related factor 2 (NRF2). Therefore, the SLC27A5 and tyrosine-metabolizing enzymes that we have identified coordinate lipid and tyrosine metabolism, regulate the cell cycle, and are potential targets for cancer treatment.