Li Zhengkun, Li Xu, Wu Shouzhen, Xue Mei, Chen Wei
Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Cancer Sci. 2014 Aug;105(8):951-5. doi: 10.1111/cas.12461.
Cancer cells preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. Emerging evidence has shown that long non-coding RNAs (lncRNAs) act as key regulators of multiple cancers. However, it remains largely unexplored whether and how lncRNA regulates glucose metabolism in cancer cells. In this study, we show that lncRNA UCA1 promotes glycolysis in bladder cancer cells, and that UCA1-induced hexokinase 2 (HK2) functions as an important mediator in this process. We further show that UCA1 activates mTOR to regulate HK2 through both activation of STAT3 and repression of microRNA143. Taken together, these findings provide the first evidence that UCA1 plays a positive role in cancer cell glucose metabolism through the cascade of mTOR-STAT3/microRNA143-HK2, and reveal a novel link between lncRNA and the altered glucose metabolism in cancer cells.
癌细胞通过有氧糖酵解优先代谢葡萄糖，这一现象被称为瓦伯格效应。新出现的证据表明，长链非编码RNA（lncRNA）是多种癌症的关键调节因子。然而，lncRNA是否以及如何调节癌细胞中的葡萄糖代谢在很大程度上仍未得到探索。在本研究中，我们表明lncRNA UCA1促进膀胱癌细胞的糖酵解，并且UCA1诱导的己糖激酶2（HK2）在这一过程中作为重要的介质发挥作用。我们进一步表明，UCA1通过激活STAT3和抑制微小RNA143来激活mTOR以调节HK2。综上所述，这些发现提供了首个证据，即UCA1通过mTOR-STAT3/微小RNA143-HK2级联在癌细胞葡萄糖代谢中发挥积极作用，并揭示了lncRNA与癌细胞中改变的葡萄糖代谢之间的新联系。
