Document Detail


Tat-activating regulatory DNA-binding protein regulates glycolysis in hepatocellular carcinoma by regulating the platelet isoform of phosphofructokinase through microRNA 520.
MedLine Citation:
PMID:  23389994     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Metabolic changes are common features of many cancer cells and are frequently associated with the clinical outcome of patients with various cancers, including hepatocellular carcinoma (HCC). Thus, aberrant metabolic pathways in cancer cells are attractive targets for cancer therapy. However, our understanding of cancer-specific regulatory mechanisms of cell metabolism is still very limited. We found that Tat-activating regulatory DNA-binding protein (TARDBP) is a novel regulator of glycolysis in HCC cells. TARDBP regulates expression of the platelet isoform of phosphofructokinase (PFKP), the rate-limiting enzyme of glycolysis that catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. Silencing of TARDBP expression in multiple HCC cell lines leads to impaired glucose metabolism and inhibition of in vitro and in vivo growth of HCC cells. Notably, the microRNA 520 (miR-520) family is an intermediate regulator of TARDBP-mediated regulation of glycolysis. Mechanistically, TARDBP suppressed expression of the miR-520 family, which, in turn, inhibited expression of PFKP. We further showed that expression of TARDBP is significantly associated with the overall survival of patients with HCC. Conclusion: Our study provides new mechanistic insights into the regulation of glycolysis in HCC cells and reveals TARDBP as a potential therapeutic target for HCC.
Authors:
Yun-Yong Park; Sang-Bae Kim; Hee Dong Han; Bo Hwa Sohn; Ji Hoon Kim; Jiyong Liang; Yiling Lu; Cristian Rodriguez-Aguayo; Gabriel Lopez-Berestein; Gordon B Mills; Anil K Sood; Ju-Seog Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-05-15
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  58     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-26     Completed Date:  2013-08-30     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  182-91     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Association for the Study of Liver Diseases.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Platelets / enzymology
Carcinoma, Hepatocellular / metabolism,  physiopathology*
Cell Line, Tumor
DNA-Binding Proteins / physiology*
Female
Glycolysis / drug effects,  genetics
Humans
Liver Neoplasms / metabolism,  physiopathology*
Mice
MicroRNAs / antagonists & inhibitors,  physiology*
Phosphofructokinase-1, Type C / genetics*
Grant Support
ID/Acronym/Agency:
5P01CA099031-07/CA/NCI NIH HHS; 5U54 CA112970-08/CA/NCI NIH HHS; CA016672/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/MIRN520 microRNA, human; 0/MicroRNAs; 0/protein TDP-43; EC 2.7.1.-/Phosphofructokinase-1, Type C
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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