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Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1A pathway
Ist Teil von
Journal of Zhejiang University. B. Science, 2023-03, Vol.24 (3), p.221-231
Ort / Verlag
Hangzhou: Zhejiang University Press
Erscheinungsjahr
2023
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (
HIF1A
) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to
HIF1A
by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of
HIF1A
overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on
HIF1A
function. The results showed that the
HIF1A
and enolase 2 (
ENO2
) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically,
HIF1A
directly binds to the DNA promoter region and upregulates the transcription of
ENO2;
ectopic expression of
ENO2
increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of
HIF1A
, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of
HIF1A
and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.