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

Yang Hsiang Lin, Meng Han Wu, Ya Hui Huang, Chau Ting Yeh, Mei Ling Cheng, Hsiang Cheng Chi, Chung Ying Tsai, I. Hsiao Chung, Ching Ying Chen, Kwang Huei Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

126 Scopus citations

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 up-regulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion, and glycolysis through suppression of microRNA (miR)-455-3p. MiR-455-3p, which is transcriptionally repressed by p21, directly targets the 3′ untranslated region of adenosine monophosphate-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. (Hepatology 2018;67:188-203).

Original languageEnglish
Pages (from-to)188-203
Number of pages16
JournalHepatology
Volume67
Issue number1
DOIs
StatePublished - 01 2018

Bibliographical note

Publisher Copyright:
© 2017 by the American Association for the Study of Liver Diseases.

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