Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) 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 HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α 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 HIF1Α function. The results showed that the HIF1Α 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, HIF1Α 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 HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α 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.
代谢重编程是癌症中一种常见的现象，而有氧糖酵解是其重要特征之一。缺氧诱导因子1亚基（HIF1Α）被认为在有氧糖酵解中发挥重要作用。柚皮苷是一种从葡萄柚和柑橘类水果中提取的天然的黄酮糖苷。在本研究中，我们通过分析结肠癌数据库，确定了与HIF1Α相关的糖酵解基因。通过进行细胞外酸化率和细胞功能的实验，证实了过表达HIF1Α对糖酵解以及结肠癌细胞增殖和迁移的调控作用。此外，我们用柚皮苷作为结肠癌细胞的抑制剂来阐明其对HIF1Α功能的影响。结果显示，结肠癌组织中HIF1Α和烯醇酶-2（ENO2）水平高度相关，其高表达提示结肠癌患者预后较差。HIF1Α直接与DNA启动子区域结合，上调ENO2的转录；而ENO2的异常表达增加了结肠癌细胞的有氧糖酵解水平。最重要的是，一定浓度的柚皮苷抑制了HIF1Α的转录活性，从而降低了结肠癌细胞的有氧糖酵解水平。总之，柚皮苷通过降低HIF1Α的转录活性来减少结肠癌细胞的糖酵解以及结肠癌细胞的增殖和侵袭。本研究有助于阐明结肠癌的进展与糖代谢之间的关系，并证明柚皮苷对结肠癌的治疗效果。.
代谢重编程是癌症中一种常见的现象，而有氧糖酵解是其重要特征之一。缺氧诱导因子1亚基（ HIF1Α）被认为在有氧糖酵解中发挥重要作用。柚皮苷是一种从葡萄柚和柑橘类水果中提取的天然的黄酮糖苷。在本研究中，我们通过分析结肠癌数据库，确定了与 HIF1Α相关的糖酵解基因。通过进行细胞外酸化率和细胞功能的实验，证实了过表达 HIF1Α对糖酵解以及结肠癌细胞增殖和迁移的调控作用。此外，我们用柚皮苷作为结肠癌细胞的抑制剂来阐明其对 HIF1Α功能的影响。结果显示，结肠癌组织中 HIF1Α和烯醇酶-2（ ENO2）水平高度相关，其高表达提示结肠癌患者预后较差。 HIF1Α直接与DNA启动子区域结合，上调 ENO2的转录；而 ENO2的异常表达增加了结肠癌细胞的有氧糖酵解水平。最重要的是，一定浓度的柚皮苷抑制了 HIF1Α的转录活性，从而降低了结肠癌细胞的有氧糖酵解水平。总之，柚皮苷通过降低 HIF1Α的转录活性来减少结肠癌细胞的糖酵解以及结肠癌细胞的增殖和侵袭。本研究有助于阐明结肠癌的进展与糖代谢之间的关系，并证明柚皮苷对结肠癌的治疗效果。
Keywords: Colon cancer; Enolase 2 (ENO2); Glycolysis; Hypoxia inducible factor-1α (HIF1Α); Metabolic reprogramming; Naringin.