miR-592/WSB1/HIF-1α axis inhibits glycolytic metabolism to decrease hepatocellular carcinoma growth.
miR-592/WSB1/HIF-1α axis inhibits glycolytic metabolism to decrease hepatocellular carcinoma growth.
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miR-592/WSB1/HIF-1 α轴抑制糖酵解代谢以减少肝细胞癌的生长
DOI：
10.18632/oncotarget.9135
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Shi L
中科院分区：
文献类型：
--
作者：
Jia YY;Zhao JY;Li BL;Gao K;Song Y;Liu MY;Yang XJ;Xue Y;Wen AD;Shi L
肝细胞癌（HCC）细胞从氧化磷酸化中迅速将其能量源转换为糖酵解代谢，以有效地增殖，但是，在这项研究中，导致该转换的分子机制仍然不清楚，我们在较差的HCC组织中却在较差的临床中降低了临床。 HCC的MiR-592的过表达在体外抑制了有氧糖酵解和HCC细胞的增殖。 ）。与WSB1基因的3'-UTR结合，从而破坏了缺氧诱导的因子1α（HIF-1α）蛋白质稳定，而HCC细胞中WSB1的过表达改善了HIF-1α的表达，葡萄糖的吸收，并提出了MIR-592的wardirition wardirient。 HCC治疗的治疗靶标。
Hepatocellular carcinoma (HCC) cells rapidly switch their energy source from oxidative phosphorylation to glycolytic metabolism in order to efficiently proliferate. However, the molecular mechanisms responsible for this switch remain unclear. In this study, we found that miR-592 was frequently downregulated in human HCC tissues and cell lines, and its downregulation was closely correlated with aggressive clinicopathological features and poor prognosis of HCC patients. Overexpression of miR-592 inhibited aerobic glycolysis and proliferation in HCC cells in vitro. Conversely, knockdown of miR-592 promoted HCC growth in both subcutaneous injection and orthotopic liver tumor implantation models in vivo. Mechanistically, miR-592 downregulation in human HCCs was correlated with an upregulation of WD repeat and SOCS box containing 1 (WSB1). We further showed that miR-592 directly binds to the 3′-UTR of the WSB1 gene, thus disrupting hypoxia inducible factor-1α (HIF-1α) protein stabilization. In turn, overexpression of WSB1 in HCC cells rescued decreased HIF-1α expression, glucose uptake, and HCC growth induced by miR-592. Collectively, our clinical data and functional studies suggest that miR-592 is a new robust inhibitor of the Warburg effect and a promising therapeutic target for HCC treatment.
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影响因子：
28.2
作者：
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影响因子：
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作者：
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