长链非编码RNA-SOX2OT通过miR-122-5p介导的丙酮酸激酶M2激活促进肝细胞癌侵袭和转移。
lncRNA-SOX2OT promotes hepatocellular carcinoma invasion and metastasis through miR-122-5p-mediated activation of PKM2.
作者信息
Liang Yingjian, Zhang Dandan, Zheng Tongsen, Yang Guangchao, Wang Jiabei, Meng Fanzheng, Liu Yao, Zhang Guoli, Zhang Linhan, Han Jihua, Hui Peng, Chen Zhengliang, Liu Yu, Wang Mingyu, Jiang Hongchi, Liu Lianxin
机构信息
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
出版信息
Oncogenesis. 2020 May 28;9(5):54. doi: 10.1038/s41389-020-0242-z.
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.
肿瘤细胞主要利用有氧糖酵解来产生能量，这一现象被称为瓦伯格效应，但瓦伯格效应在肝癌细胞转移中的作用尚未完全明确。在本研究中，我们的结果表明葡萄糖代谢水平与肝细胞癌（HCC）的转移潜能之间呈正相关。我们还观察到，一种长链非编码RNA-SOX2OT（lncRNA-SOX2OT）不仅可以增加HCC的转移潜能，还能促进丙酮酸激酶M2（PKM2）介导的葡萄糖代谢激活。在HCC细胞中抑制PKM2会极大地削弱lncRNA-SOX2OT对瓦伯格效应和转移的促进作用。此外，发现miR-122-5p是lncRNA-SOX2OT调节PKM2表达的直接靶点。因此，我们的研究结果表明，作为PKM2的调节因子，lncRNA-SOX2OT可能使HCC患者易发生转移，并可能作为HCC患者转移预测和治疗的候选靶点。
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