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: Mechanistically, UCA1 exerts its role in glycolysis by upregulation of HK2, a key glycolytic enzyme and pivotal player in the Warburg effect.(17) We then showed that inactivation of mTOR by rapamycin fully attenuated the effect of UCA1 on glycolysis in bladder cancer cells. We found that two signals control the regulation of HK2 by UCA1 through the mTOR pathway. First, UCA1 facilitates the activation of STAT3, which promotes the transcription of HK2. Second, UCA1 represses miR143 and subsequently restores HK2 expression at the post-transcriptional level. Without the activation of STAT3, there is insufficient HK2 mRNA; however, without repression of miR143, increased mRNA levels of HK2 by UCA1/mTOR/STAT3 do not result in more HK2 proteins. The importance of this dual-control system is reflected by the results that both activation of STAT3 and repression of miR143 are required for UCA1 to accelerate glycolysis in bladder cancer cells. Thus, our findings reveal a novel UCA1–mTOR–STAT3/miR143–HK2 axis that links lncRNA and glucose metabolism in cancer cells (Fig. 5).
Affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.