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: As recent findings suggested that miRNA143 (miR143), which is downregulated by mTOR activation, reduced glucose metabolism and inhibited cancer cell proliferation and tumor formation through targeting HK2,(21,27) we tested whether this regulation also extends to UCA1. Indeed, we found that miR143 expression was inversely correlated with UCA1 in stable cell lines (Fig. 4a,b), whereas rapamycin increased miR143 levels suppressed by UCA1 (Fig. 4c). We also found that the miR143 mimic significantly reduced the protein levels of HK2 (Fig. 4d), whereas miR143 inhibitor led to enhanced HK2 expression (Fig. 4e). These results suggested that UCA1 uses an additional mechanism to positively regulate HK2 protein expression at the post-transcriptional level.
Affiliation: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.