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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| Format: | Article |
| Language: | English |
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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
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| 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. |
| format | Article |
| id | doaj-art-b42efbd81b7c416fa9b0d9322ecf054d |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| 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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