Tat-activating regulatory DNA-binding protein regulates glycolysis in hepatocellular carcinoma by regulating the platelet isoform of phosphofructokinase through microRNA 520

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

    Research output: Contribution to journalArticle

    44 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)182-191
    Number of pages10
    JournalHepatology
    Volume58
    Issue number1
    DOIs
    StatePublished - Jul 1 2013

    ASJC Scopus subject areas

    • Hepatology

    Fingerprint Dive into the research topics of 'Tat-activating regulatory DNA-binding protein regulates glycolysis in hepatocellular carcinoma by regulating the platelet isoform of phosphofructokinase through microRNA 520'. Together they form a unique fingerprint.

  • Cite this

    Park, Y. Y., Kim, S. B., Han, H. D., Sohn, B. H., Kim, J. H., Liang, J., Lu, Y., Rodriguez-Aguayo, C., Lopez-Berestein, G., Mills, G. B., Sood, A. K., & Lee, J. S. (2013). Tat-activating regulatory DNA-binding protein regulates glycolysis in hepatocellular carcinoma by regulating the platelet isoform of phosphofructokinase through microRNA 520. Hepatology, 58(1), 182-191. https://doi.org/10.1002/hep.26310