BACKGROUND Histone lysine demethylase 4B (KDM4B) has been implicated in various pathological processes and human diseases. Glucose metabolism is the main pattern of energy supply in cells and its dysfunction is closely related to tumorigenesis. Recent study shows that KDM4B protects against obesity and metabolic dysfunction. We realized the significant role of KDM4B in metabolism. However, the role of KDM4B in glucose metabolism remains unclear. Here, we sought to delineate the role and mechanism of KDM4B in glucose metabolism in colorectal cancer (CRC). METHODS We first analyzed the role of KDM4B in glucose uptake and CRC growth. We then investigated the consequences of KDM4B inhibition on the expression of GLUT1 and AKT signaling, also explored the underlying mechanism. Finally, we detected the mechanism in vivo and assessed the potential correlation between the expression of KDM4B and CRC prognosis. RESULTS We found that KDM4B promoted glucose uptake and ATP production by regulating the expression of GLUT1 via the AKT signaling pathway. KDM4B could interact with TRAF6 and promote TRAF6-mediated ubiquitination of AKT for AKT activation. Furthermore, we demonstrated that KDM4B was overexpressed in CRC specimens and high level of KDM4B was associated with a poor survival rate in CRC patients. CONCLUSIONS These findings reveal that KDM4B plays an important role in promoting CRC progression by enhancing glucose metabolism.

中文翻译：

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KDM4B通过刺激TRAF6介导的AKT激活，促进结直肠癌的生长和葡萄糖代谢。

背景技术组蛋白赖氨酸脱甲基酶4B（KDM4B）已经牵涉到各种病理过程和人类疾病中。葡萄糖代谢是细胞中能量供应的主要方式，其功能障碍与肿瘤发生密切相关。最近的研究表明，KDM4B可防止肥胖和代谢功能障碍。我们意识到KDM4B在代谢中的重要作用。但是，KDM4B在葡萄糖代谢中的作用仍不清楚。在这里，我们试图描述KDM4B在大肠癌（CRC）葡萄糖代谢中的作用和机制。方法我们首先分析了KDM4B在葡萄糖摄取和CRC生长中的作用。然后，我们研究了KDM4B抑制对GLUT1和AKT信号表达的影响，并探讨了其潜在机制。最后，我们检测了体内机制，并评估了KDM4B表达与CRC预后之间的潜在相关性。结果我们发现KDM4B通过AKT信号通路调节GLUT1的表达来促进葡萄糖的摄取和ATP的产生。KDM4B可以与TRAF6相互作用，并促进TRAF6介导的AKT泛素化以激活AKT。此外，我们证明了KDM4B在CRC标本中过表达，而高水平的KDM4B与CRC患者的不良生存率相关。结论这些发现表明，KDM4B通过增强葡萄糖代谢在促进CRC进展中起重要作用。KDM4B可以与TRAF6相互作用，并促进TRAF6介导的AKT泛素化以激活AKT。此外，我们证明了KDM4B在CRC标本中过表达，而高水平的KDM4B与CRC患者的不良生存率相关。结论这些发现表明，KDM4B通过增强葡萄糖代谢在促进CRC进展中起重要作用。KDM4B可以与TRAF6相互作用，并促进TRAF6介导的AKT泛素化以激活AKT。此外，我们证明了KDM4B在CRC标本中过表达，而高水平的KDM4B与CRC患者的不良生存率相关。结论这些发现表明，KDM4B通过增强葡萄糖代谢在促进CRC进展中起重要作用。