한빛사논문
Yun-Yong Park1, Sang Bae Kim1, Hee Dong Han2,6, Bo-Hwa Sohn1, Ji-Hoon Kim1,7, Jiyong Liang1, Yiling Lu1, Gordon B. Mills1, Anil K. Sood2,3,4,5, Ju-Seog Lee1,8,*
1Department of Systems Biology, 2Department of Gynecologic Oncology, 3Department of Experimental Therapeutics, 4Department of Cancer Biology and 5Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 6Research Center for Medicinal Chemistry, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Deajeon 305-600, South Korea. 7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University School of Medicine, Seoul, Korea. 8Department of Biochemistry and Molecular Biology, Medical Research Center and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
*Corresponding author : Ju-Seog Lee
Department of Systems Biology, Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Abstract
Metabolic changes are common features of many cancer cells and are frequently associated with the clinical outcome of patientswith 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 glycolysisthat 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 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. (HEPATOLOGY 2013.)
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