Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line

Colorectal cancer (CRC) is one of the most common malignant neoplasms in the world, and is characterized by a high mortality rate. The study of the key aspects of colorectal cancer formation and progression is necessary to develop new approaches to its therapy, as well as to search for new diagnosti...

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Main Authors: M. S. Fedorova, I. Y. Karpova, A. V. Lipatova, E. A. Pudova, Z. G. Guvatova, D. V. Kochetkov, A. V. Chaika, B. Y. Alekseev, M. V. Kiseleva, A. D. Kaprin, A. V. Kudryavtseva, A. V.  Snezhkina
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2018-01-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/1270
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author M. S. Fedorova
I. Y. Karpova
A. V. Lipatova
E. A. Pudova
Z. G. Guvatova
D. V. Kochetkov
A. V. Chaika
B. Y. Alekseev
M. V. Kiseleva
A. D. Kaprin
A. V. Kudryavtseva
A. V.  Snezhkina
author_facet M. S. Fedorova
I. Y. Karpova
A. V. Lipatova
E. A. Pudova
Z. G. Guvatova
D. V. Kochetkov
A. V. Chaika
B. Y. Alekseev
M. V. Kiseleva
A. D. Kaprin
A. V. Kudryavtseva
A. V.  Snezhkina
author_sort M. S. Fedorova
collection DOAJ
description Colorectal cancer (CRC) is one of the most common malignant neoplasms in the world, and is characterized by a high mortality rate. The study of the key aspects of colorectal cancer formation and progression is necessary to develop new approaches to its therapy, as well as to search for new diagnostic, prognostic and predictive biomarkers of CRC. In many types of tumors, one of the key changes in metabolism is the  activation of glycolysis, which is associated with alterations in the expression of the main glycolytic enzymes and regulatory molecules. There is often an increase in hexokinase 2 (HK2) exogenous expression in tumor cells, which makes it a promising target for anticancer therapy. Quantitative expression analysis of 15 genes (GAPDH, ADPGK, ALDOA, ENO3, PFKL, PGK1, PGAM1, PKM2, ENO1, PDK1, PDK3, PFKP, ENO2, GPI, and BPGM), encoding the key glycolysis enzymes, as well as HIF1A gene was carried out in a modified RKO cell line, which constantly expresses the short hairpin RNA (shRNA) for the inhibition of hexokinase 2. A significant decrease in the expression of PFKP, BPGM, and GPI genes both at the mRNA (5­, 86­, and 93­fold, respectively) and protein (2.5­, 3.5­, and 19­fold, respectively) levels was revealed. Probably, the downregulation of GPI and PFKP is associated with a decrease in the amount of their substrates, glucose­6­phosphate and fructose6­phosphate, under the inhibition of hexokinase 2. Nevertheless, the cause of a decreased mRNA level of these three enzymes, while the expression level of other glycolytic participants is constant, requires further investigation.
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spelling doaj-art-b42efbd81b7c416fa9b0d9322ecf054d2025-02-01T09:58:05ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592018-01-0121893293610.18699/VJ17.315704Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell lineM. S. Fedorova0I. Y. Karpova1A. V. Lipatova2E. A. Pudova3Z. G. Guvatova4D. V. Kochetkov5A. V. Chaika6B. Y. Alekseev7M. V. Kiseleva8A. D. Kaprin9A. V. Kudryavtseva10A. V.  Snezhkina11Engelhardt Institute of Molecular Biology RAS.Engelhardt Institute of Molecular Biology RAS.Engelhardt Institute of Molecular Biology RAS.Engelhardt Institute of Molecular Biology RAS.Engelhardt Institute of Molecular Biology RAS.Engelhardt Institute of Molecular Biology RAS.National Medical Research Radiological Center, Ministry of Health of the Russian Federation.National Medical Research Radiological Center, Ministry of Health of the Russian Federation.National Medical Research Radiological Center, Ministry of Health of the Russian Federation.National Medical Research Radiological Center, Ministry of Health of the Russian Federation.Engelhardt Institute of Molecular Biology RAS; National Medical Research Radiological Center, Ministry of Health of the Russian Federation.Engelhardt Institute of Molecular Biology RAS.Colorectal cancer (CRC) is one of the most common malignant neoplasms in the world, and is characterized by a high mortality rate. The study of the key aspects of colorectal cancer formation and progression is necessary to develop new approaches to its therapy, as well as to search for new diagnostic, prognostic and predictive biomarkers of CRC. In many types of tumors, one of the key changes in metabolism is the  activation of glycolysis, which is associated with alterations in the expression of the main glycolytic enzymes and regulatory molecules. There is often an increase in hexokinase 2 (HK2) exogenous expression in tumor cells, which makes it a promising target for anticancer therapy. Quantitative expression analysis of 15 genes (GAPDH, ADPGK, ALDOA, ENO3, PFKL, PGK1, PGAM1, PKM2, ENO1, PDK1, PDK3, PFKP, ENO2, GPI, and BPGM), encoding the key glycolysis enzymes, as well as HIF1A gene was carried out in a modified RKO cell line, which constantly expresses the short hairpin RNA (shRNA) for the inhibition of hexokinase 2. A significant decrease in the expression of PFKP, BPGM, and GPI genes both at the mRNA (5­, 86­, and 93­fold, respectively) and protein (2.5­, 3.5­, and 19­fold, respectively) levels was revealed. Probably, the downregulation of GPI and PFKP is associated with a decrease in the amount of their substrates, glucose­6­phosphate and fructose6­phosphate, under the inhibition of hexokinase 2. Nevertheless, the cause of a decreased mRNA level of these three enzymes, while the expression level of other glycolytic participants is constant, requires further investigation.https://vavilov.elpub.ru/jour/article/view/1270colorectal cancershrnaqpcrwestern blotglycolysiswarburg effecthk2
spellingShingle M. S. Fedorova
I. Y. Karpova
A. V. Lipatova
E. A. Pudova
Z. G. Guvatova
D. V. Kochetkov
A. V. Chaika
B. Y. Alekseev
M. V. Kiseleva
A. D. Kaprin
A. V. Kudryavtseva
A. V.  Snezhkina
Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line
Вавиловский журнал генетики и селекции
colorectal cancer
shrna
qpcr
western blot
glycolysis
warburg effect
hk2
title Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line
title_full Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line
title_fullStr Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line
title_full_unstemmed Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line
title_short Knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell line
title_sort knockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes pfkp bpgm and gpi in rko cell line
topic colorectal cancer
shrna
qpcr
western blot
glycolysis
warburg effect
hk2
url https://vavilov.elpub.ru/jour/article/view/1270
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