Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR-STAT3/microRNA143 pathway.
Bottom Line: Emerging evidence has shown that long non-coding RNAs (lncRNAs) act as key regulators of multiple cancers.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.
Affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.Show MeSH
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Mentions: To probe the potential mechanism by which UCA1 regulates glycolysis in bladder cancer cells, we examined the effects of UCA1 on the expression of HK2. Quantitative PCR analyses showed that HK2 mRNA levels were upregulated by UCA1 (Fig. 2a). In line with these results, Western blot assays showed that UCA1 enhanced HK2 protein expression (Fig. 2b). Moreover, both HK2 mRNA and protein levels were significantly reduced by knockdown of UCA1 (Fig. 2c,d). Given that HK2 is a critical enzyme catalyzing the first and irreversible step of glycolysis,(16) and that its expression is most significantly regulated by UCA1, we reasoned that HK2 upregulation likely plays a major role in the enhancement of glucose consumption and lactate production under such conditions. Indeed, knockdown of HK2 significantly attenuated the effect of UCA1 on glucose consumption and lactate production (Fig. 2e,f). We thus focused on the regulation of HK2 for further mechanistic studies.
Affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.