Heparin treatment increases thioredoxin interacting protein expression in hepatocellular carcinoma cells
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Heparin treatment increases thioredoxin interacting protein expression in hepatocellular carcinoma cells. / Gunes, Aysim; Iscan, Evin; Topel, Hande; Avci, Sanem Tercan; Gumustekin, Mukaddes; Erdal, Esra; Atabey, Nese.
In: The International Journal of Biochemistry & Cell Biology, Vol. 65, 08.2015, p. 169-81.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Heparin treatment increases thioredoxin interacting protein expression in hepatocellular carcinoma cells
AU - Gunes, Aysim
AU - Iscan, Evin
AU - Topel, Hande
AU - Avci, Sanem Tercan
AU - Gumustekin, Mukaddes
AU - Erdal, Esra
AU - Atabey, Nese
N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.
PY - 2015/8
Y1 - 2015/8
N2 - Heparins play an important role in cell growth, differentiation, migration and invasion. However, the molecular mechanisms of heparin mediated cellular behaviors are not well defined. To determine the effect of heparin on gene expression, we performed a cDNA microarray in a hepatocellular carcinoma cell line and found that heparin regulates transcription of genes involved in glucose metabolism. In this study, we showed a new role of heparin in the regulation of thioredoxin interacting protein, which is a major regulator of glucose metabolism, in hepatocellular carcinoma cell lines. We determined the importance of a unique carbohydrate response element located on its promoter for the heparin-induced activation of thioredoxin-interacting protein and the modulatory role of heparin on nuclear accumulation of carbohydrate response element associated proteins. We showed the importance of heparin mediated histone modifications and down-regulation of Enhancer of zeste 2 polycomb repressive complex 2 expression for heparin mediated overexpression of thioredoxin-interacting protein. When we tested biological significance of these data; we observed that cells overexpressing thioredoxin-interacting protein are less adhesive and proliferative, however they have a higher migration and invasion ability. Interestingly, heparin treatment increased thioredoxin-interacting protein expression in liver of diabetic rats. In conclusion, our results show that heparin activates thioredoxin-interacting protein expression in liver and hepatocellular carcinoma cells and provide the first evidences of regulatory roles of heparin on carbohydrate response element associated factors. This study will contribute future understanding of the effect of heparin on glucose metabolism and glucose independent overexpression of thioredoxin-interacting protein during hepatocarcinogenesis.
AB - Heparins play an important role in cell growth, differentiation, migration and invasion. However, the molecular mechanisms of heparin mediated cellular behaviors are not well defined. To determine the effect of heparin on gene expression, we performed a cDNA microarray in a hepatocellular carcinoma cell line and found that heparin regulates transcription of genes involved in glucose metabolism. In this study, we showed a new role of heparin in the regulation of thioredoxin interacting protein, which is a major regulator of glucose metabolism, in hepatocellular carcinoma cell lines. We determined the importance of a unique carbohydrate response element located on its promoter for the heparin-induced activation of thioredoxin-interacting protein and the modulatory role of heparin on nuclear accumulation of carbohydrate response element associated proteins. We showed the importance of heparin mediated histone modifications and down-regulation of Enhancer of zeste 2 polycomb repressive complex 2 expression for heparin mediated overexpression of thioredoxin-interacting protein. When we tested biological significance of these data; we observed that cells overexpressing thioredoxin-interacting protein are less adhesive and proliferative, however they have a higher migration and invasion ability. Interestingly, heparin treatment increased thioredoxin-interacting protein expression in liver of diabetic rats. In conclusion, our results show that heparin activates thioredoxin-interacting protein expression in liver and hepatocellular carcinoma cells and provide the first evidences of regulatory roles of heparin on carbohydrate response element associated factors. This study will contribute future understanding of the effect of heparin on glucose metabolism and glucose independent overexpression of thioredoxin-interacting protein during hepatocarcinogenesis.
KW - Amino Acid Sequence
KW - Animals
KW - Carcinoma, Hepatocellular/drug therapy
KW - Carrier Proteins/biosynthesis
KW - Cell Line, Tumor
KW - Diabetes Mellitus, Experimental/genetics
KW - Disease Models, Animal
KW - Heparin/pharmacology
KW - Humans
KW - Liver Neoplasms/drug therapy
KW - Male
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Promoter Regions, Genetic
KW - Rats
KW - Rats, Wistar
KW - Transcriptional Activation/drug effects
KW - Transfection
U2 - 10.1016/j.biocel.2015.05.025
DO - 10.1016/j.biocel.2015.05.025
M3 - Journal article
C2 - 26037596
VL - 65
SP - 169
EP - 181
JO - International Journal of Biochemistry & Cell Biology
JF - International Journal of Biochemistry & Cell Biology
SN - 1357-2725
ER -
ID: 389913966