Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of taurine up‐regulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion, and glycolysis through suppression of microRNA (miR)‐455‐3p. MiR‐455‐3p, which is transcriptionally repressed by p21, directly targets the 3′ untranslated region of adenosine monophosphate‐activated protein kinase subunit beta 2 (AMPKβ2). The TUG1/miR‐455‐3p/AMPKβ2 axis regulates cell growth, metastasis, and glycolysis through regulation of hexokinase 2 (HK2). TUG1 is clearly associated with HK2 overexpression and unfavorable prognosis in HCC patients. Conclusion: Our data collectively highlight that novel regulatory associations among TUG1, miR‐455‐3p, AMPKβ2, and HK2 are an important determinant of glycolytic metabolism and metastasis in HCC cells and support the potential utility of targeting TUG1/HK2 as a therapeutic strategy for HCC. (Hepatology 2018;67:188‐203)

中文翻译：

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牛磺酸上调基因1作为协调肝细胞癌糖酵解和转移的主要调节因子

癌细胞显示出改变的葡萄糖代谢，其特征是偏好有氧糖酵解。肝细胞癌 (HCC) 的有氧糖酵解表型通常与肿瘤进展和较差的临床结果相关。然而，糖酵解代谢是否影响 HCC 转移的问题仍不清楚。在目前的研究中，我们发现牛磺酸上调基因 1 (TUG1) 的敲低通过抑制 microRNA (miR)-455-3p 显着抑制细胞迁移、侵袭和糖酵解。MiR-455-3p 被 p21 转录抑制，直接靶向单磷酸腺苷活化蛋白激酶亚基 2 (AMPKβ2) 的 3' 非翻译区。TUG1/miR-455-3p/AMPKβ2 轴通过调节己糖激酶 2 (HK2) 来调节细胞生长、转移和糖酵解。TUG1 显然与 HCC 患者的 HK2 过表达和不良预后相关。结论：我们的数据共同强调了 TUG1、miR-455-3p、AMPKβ2 和 HK2 之间的新调控关联是 HCC 细胞糖酵解代谢和转移的重要决定因素，并支持靶向 TUG1/HK2 作为治疗策略的潜在效用。肝细胞癌。（肝病学 2018 年；67：188-203）