摘要Hepatocellular carcinoma(HCC)remains the third leading cause of cancer-related deaths worldwide;however,its therapeutic options are limited.Understanding the molecular mechanisms of HCC could provide insight into new therapies.Emerging studies indicate the important role of long-noncoding RNAs(lncRNAs)in the pathogenesis of HCC.The expression of the well-studied lncRNA taurine upregulated gene 1(TUG1)is upregulated in HCC tissues,but its transcriptomic effects in HCC cells remain unexplored.We established TUG1-knockdown and control HCC cells for RNA-seq experiments.KEGG analysis revealed glycolysis as the top enriched pathway upon TUG1 silencing.Accordingly,TUG1-depleted HCC cells showed impairments in glucose uptake,ATP synthesis,and lactate production.Clinical HCC tissue data revealed positive gene expression correlations between TUG1 and several glycolysis-related genes.To identify a molecular function of TUG1 in glycolysis,we explored the competing endogenous model and used bioinformatic tools to find the five microRNAs(miRNAs)that had the most binding sites for TUG1.Among these miRNAs,miR-122-5p exhibited an inverse correlation in gene expression with most TUG1-regulated glycolysis genes,including PKM,ALDOA,ENO2,and PFKM.Dual-luciferase assays demonstrated the direct interaction between TUG1 and miR-122-5p and between miR-122-5p and the 3'untranslated regions of both PKM and ALDOA.We further showed that inhibition of miR-122-5p alleviated the suppression of glycolysis induced by TUG1 depletion.Together,our RNA-seq analysis of TUG1-depleted HCC cells,combined with clinical data,reveals a critical role of TUG1 in regulating glycolysis and provides new insight into its oncogenic function in HCC.