Regulation of glucose metabolism in hepatocarcinogenesis by microRNAs

Abstract

In the past decade, considerable effort has been made in elucidating the mechanism underlying the high level of aerobic glycolysis in cancer cells. While some recent studies have attempted to address this issue, the potential role of microRNAs in this process has not been explored until recently. These studies have demonstrated involvement of just five deregulated miRNAs in glucose metabolism in hepatocarcinogenesis. This review discusses the metabolic significance of these miRNAs in hepatoceullular carcinoma, their targets in glycolysis, gluconeogenesis, and pentose phosphate pathways, and provides an insight into the therapeutic potential of targeting specific miRNAs.

Figure 1

MicroRNA-mediated metabolism. The figure shows aspects of microRNA-mediated glucose and glutamine metabolism in cancer. Black arrows show the catabolic and anabolic processing of metabolites. The larger black arrows represent pathways that are upregulated in HCC, and the broken arrows signify that metabolic intermediates are not shown. MicroRNAs in blue are downregulated in HCC, and those in orange are upregulated. MicroRNA-mediated regulations are shown in red for inhibition and green for activation. The broken arrows represent mechanisms in which the microRNA does not directly target an enzyme within the specified metabolic pathway. The question marks next to some of the miR-155 regulations indicate mechanisms that are yet to be elucidated. GLUT, glucose transporter; MCT4, monocarboxylate transporter 4; G6PD, glucose-6-phosphate dehydrogenase; TKT, transketolase.