Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies with a hallmark of aberrant metabolism. The mechanism of long noncoding RNAs (lncRNAs) underlying the aggressive behaviors and glycolysis of HCC is poorly understood. In this study, we identified, via microarray, novel lncRNA NONHSAT024276 as a potential tumor suppressor in HCC. The downregulation of NONHSAT024276 closely correlated with larger tumor volume and higher aspartate transaminase levels. Functional experiments were performed to verify the role of NONHSAT024276 in HCC progression, and the negative effects of NONHSAT024276 expression on cell proliferation and migration were identified. Mechanistically, NONHSAT024276 directly bound to polypyrimidine tract-binding protein 1 (PTBP1), downregulating it and forming a feedback loop. Furthermore, NONHSAT024276 increased the ratio of M1 and M2 isoforms of pyruvate kinase (PKM1/PKM2) and also obstructed the PTBP1/PKM-mediated glycolysis. Finally, the rescue assays confirmed that NONHSAT024276 functioned in HCC via downregulating PTBP1 to increase the PKM1/PKM2 ratio. Hence, this study supported a model in which NONHSAT024276 downregulated PTBP1 and formed a feedback loop to increase the PKM1/PKM2 ratio to inhibit glycolysis and progression of HCC, opening new prospects for preventing or treating HCC.
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