vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ17.315vavilov-1270Research ArticleСИСТЕМНАЯ БИОЛОГИЯ И БИОМЕДИЦИНАSYSTEMS BIOLOGY AND BIOMEDICINEИнгибирование гексокиназы 2 приводит к снижению экспрессии ферментов гликолиза PFKP, BPGM и GPI в клеточной линии RKOKnockdown of hexokinase 2 results in a decreased expression level of the glycolytic enzymes PFKP, BPGM, and GPI in RKO cell lineФедороваМ. С.FedorovaM. S.

Москва.

Moscow.

КарповаИ. Ю.KarpovaI. Y.

Москва.

Moscow.

ЛипатоваА. В.LipatovaA. V.

Москва.

Moscow.

ПудоваЕ. А.PudovaE. A.

Москва.

Moscow.

ГуватоваЗ. Г.GuvatovaZ. G.

Москва.

Moscow.

КочетковД. В.KochetkovD. V.

Москва.

Moscow.

ЧайкаА. В.ChaikaA. V.

Москва.

Moscow.

АлексеевБ. Я.AlekseevB. Y.

Москва.

Moscow.

КиселеваМ. В.KiselevaM. V.

Москва.

Moscow.

КапринА. Д.KaprinA. D.

Москва.

Moscow.

КудрявцеваА. В.KudryavtsevaA. V.

Москва.

Moscow.

rhizamoeba@mail.ruСнежкинаА. В. SnezhkinaA. V.

Москва.

Moscow.

Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук.РоссияEngelhardt Institute of Molecular Biology RAS.Russian FederationНациональный медицинский исследовательский центр радиологии Министерства здравоохранения Российской Федерации.РоссияNational Medical Research Radiological Center, Ministry of Health of the Russian Federation.Russian FederationИнститут молекулярной биологии им. В.А. Энгельгардта Российской академии наук; Национальный медицинский исследовательский центр радиологии Министерства здравоохранения Российской Федерации.РоссияEngelhardt Institute of Molecular Biology RAS; National Medical Research Radiological Center, Ministry of Health of the Russian Federation.Russian Federation201720012018218932936Copyright © Федорова М.С., Карпова И.Ю., Липатова А.В., Пудова Е.А., Гуватова З.Г., Кочетков Д.В., Чайка А.В., Алексеев Б.Я., Киселева М.В., Каприн А.Д., Кудрявцева А.В., Снежкина А.В., 20182018Федорова М.С., Карпова И.Ю., Липатова А.В., Пудова Е.А., Гуватова З.Г., Кочетков Д.В., Чайка А.В., Алексеев Б.Я., Киселева М.В., Каприн А.Д., Кудрявцева А.В., Снежкина А.В.Fedorova M.S., Karpova I.Y., Lipatova A.V., Pudova E.A., Guvatova Z.G., Kochetkov D.V., Chaika A.V., Alekseev B.Y., Kiseleva M.V., Kaprin A.D., Kudryavtseva A.V.,  Snezhkina A.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1270

Колоректальный рак (КРР) – одно из наиболее распространенных злокачественных новообразований в мире, характеризующееся высоким уровнем смертности. Изучение ключевых аспектов формирования и прогрессии КРР необходимо для разработки новых подходов к его терапии, а также поиска новых диагностических, прогностических и предиктивных биомаркеров. Для многих видов опухолей важным изменением метаболизма является акти ва ция гликолиза, ассоциированная с нарушением экспрессии основных ферментов, принимающих участие в этом процессе, и регуляторных молекул. Чаще всего в опухолевых клетках наблюдается повышение экспрессии гексокиназы 2 (HK2), что делает ее многообещающей мишенью для таргетной терапии. В мо дифицированной нами клеточной линии RKO, постоянно экспрес сирующей короткие шпилечные РНК для ингибирования гексоки назы 2, проведен количественный анализ экспрессии 15 генов (GAPDH, ADPGK, ALDOA, ENO3, PFKL, PGK1, PGAM1, PKM2, ENO1, PDK1, PDK3, PFKP, ENO2, GPI и BPGM), кодирующих ключевые ферменты гликолиза, а также гена HIF1A. Выявлено значительное снижение экспрессии генов PFKP, BPGM и GPI на уровне мРНК (в 5, 86 и 93 раза соответственно) и белка (в 2.5, 3.5 и 19 раз соответственно). Вероятно, снижение экспрессии GPI и PFKP связано с уменьшением количества их субстратов, глюкозо­6­фосфата и фруктозо­6­фосфата, при подавлении гексокиназы 2. Однако вопрос о при чинах снижения уровня мРНК этих трех ферментов при одновременном сохранении уровня экспрессии других участников гликолиза требует дальнейшего изучения.

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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The authors declare that there are no conflicts of interest present.