Taurine up-regulated 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 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).

• Authors: 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
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 67 Issue 1 Pg. 188-203 (01 2018) ISSN: 1527-3350 [Electronic] United States
• PMID: 28802060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 by the American Association for the Study of Liver Diseases.

Chemical References

• MicroRNAs
• RNA, Long Noncoding
• TUG1 long noncoding RNA, human
• Taurine

Topics

• Biopsy, Needle
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Glycolysis (genetics)
• Humans
• Immunohistochemistry
• Liver Neoplasms (genetics, pathology)
• Male
• MicroRNAs (genetics)
• Neoplasm Metastasis (genetics)
• RNA, Long Noncoding (genetics)
• Real-Time Polymerase Chain Reaction
• Sensitivity and Specificity
• Signal Transduction (drug effects)
• Taurine (pharmacology)
• Up-Regulation