Aerobic glycolysis (the Warburg effect) facilitates tumor growth, and drugs targeting aerobic glycolysis are being developed. However, how the Warburg effect is directly regulated is largely unknown. Here we show that transcription factor SIX1 directly increases the expression of many glycolytic genes, promoting the Warburg effect and tumor growth in vitro and in vivo. SIX1 regulates glycolysis through HBO1 and AIB1 histone acetyltransferases. Cancer-related SIX1 mutation increases its ability to promote aerobic glycolysis and tumor growth. SIX1 glycolytic function is directly repressed by microRNA-548a-3p, which is downregulated, inversely correlates with SIX1, and is a good predictor of prognosis in breast cancer patients. Thus, the microRNA-548a-3p/SIX1 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising cancer therapeutic target.

中文翻译：

---

SIX1对癌症中的Warburg效应的转录调控。

有氧糖酵解（Warburg效应）促进肿瘤生长，并且正在开发针对有氧糖酵解的药物。但是，如何直接调节Warburg效应尚不清楚。在这里，我们显示了转录因子SIX1直接增加了许多糖酵解基因的表达，从而在体外和体内促进了Warburg效应和肿瘤的生长。SIX1通过HBO1和AIB1组蛋白乙酰转移酶调节糖酵解。癌症相关的SIX1突变增强了其促进有氧糖酵解和肿瘤生长的能力。SIX1的糖酵解功能被下调的microRNA-548a-3p直接抑制，与SIX1呈负相关，并且是乳腺癌患者预后的良好预测指标。因此，