Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR-STAT3/microRNA143 pathway.
Bottom Line: 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.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: Our previous studies showed that UCA1 played a pivotal role in bladder cancer progression by activating the PI3K–Akt–mTOR pathway.(13) In addition, a recent study showed that STAT3 is a direct transcriptional activator for HK2.(21) Taking into account that STAT3 is a known downstream effector of mTOR,(22,23) we speculated that the UCA1 upregulated HK2 through activation of mTOR–STAT3 signaling. As expected, we found that the phosphorylation of STAT3 was positively related to UCA1 in stable cell lines (Fig. 3a,b). Furthermore, HK2 mRNA levels were reduced by rapamycin (Fig. 3c), whereas knockdown of STAT3 completely abolished the induction of HK2 transcript levels (Fig. 3f). Consistent with an important role of the mTOR–STAT3 pathway in mediating the upregulation of HK2 transcription by UCA1, we found that the rates of glucose consumption and lactate production were significantly decreased by rapamycin or STAT3 siRNA (Fig. 3d,e,g,h). Collectively, these results reveal that UCA1 promotes HK2 mRNA transcription through activation of the mTOR–STAT3 pathway.
Affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.