Taurine upregulated gene 1 functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma

Abstract

Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of Taurine upregulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion and glycolysis via suppression of miR-455-3p. MiR-455-3p, which is transcriptionally repressed by p21, directly targets the 3′-untranslated region (UTR) of AMP-activated protein kinase subunit beta 2 (AMPKβ2). The TUG1/miR-455-3p/AMPKβ2 axis regulates cell growth, metastasis and glycolysis through regulation of Hexokinase 2 (HK2). TUG1 is clearly associated with HK2 overexpression and unfavorable prognosis in HCC patients. Conclusion: Our data collectively highlight that novel regulatory associations among TUG1, miR-455-3p, AMPKβ2 and HK2 are an important determinant of glycolytic metabolism and metastasis in HCC cells and support the potential utility of targeting TUG1/HK2 as a therapeutic strategy for HCC. This article is protected by copyright. All rights reserved.

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