Abstract
Tumor cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect, but the involvement of Warburg effect in liver cancer cell metastasis is not well understood. In present study, our results indicate a positive correlation between glucose metabolism level and metastatic potential of hepatocellular carcinoma (HCC). We also observed that a long noncoding RNA-SOX2OT (lncRNA-SOX2OT) can not only increase the metastatic potential of HCC but also promote a pyruvate kinase M2 (PKM2)-mediated activation of glucose metabolism. Inhibition of PKM2 in HCC cells greatly compromises lncRNA-SOX2OT in promoting Warburg effect and metastasis. Furthermore, miR-122-5p was found being a direct target of lncRNA-SOX2OT in regulating PKM2 expression. Thus, our findings reveal that lncRNA-SOX2OT, a regulator of PKM2, could predispose HCC patients to metastases and may serve as a candidate for metastatic prediction and therapies in HCC patients.
Highlights
Hepatocellular carcinoma (HCC) is a common and aggressive human malignancy[1,2], with a dismal outcome that is largely due to metastasis and postsurgical recurrence
SUVmax levels were significantly higher in metastatic liver tissues than in nonmetastatic hepatocellular carcinoma (HCC) tissues (Fig. 1b and Fig. S1A), indicating that liver cancer with a high level of glucose metabolism may have greater metastatic potential
This notion is consistent with the reprogrammed energy metabolism characteristic of cancer cells which termed “aerobic glycolysis”[8]
Summary
Hepatocellular carcinoma (HCC) is a common and aggressive human malignancy[1,2], with a dismal outcome that is largely due to metastasis and postsurgical recurrence. The 5-year survival rate of HCC patients remains poor[3]. Novel molecular mechanisms that can help determine how HCC metastasizes and improve treatment are still urgently needed. Cancer metabolic reprogramming has been recognized as one of the ten cancer hallmarks[4]. Cancer cells favor the shift to glycolytic metabolism, referred to as the “Warburg effect”, a phenomenon whereby cancer cells rely mainly on aerobic glycolysis to generate adenosine triphosphate (ATP) even in the presence of O25–8. The Warburg effect promotes the growth and metastasis of tumors[9,10,11,12]
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