The oncoprotein HBXIP promotes glucose metabolism reprogramming via downregulating SCO2 and PDHA1 in breast cancer.
The oncoprotein HBXIP promotes glucose metabolism reprogramming via downregulating SCO2 and PDHA1 in breast cancer.
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癌蛋白 HBXIP 通过下调乳腺癌中 SCO2 和 PDHA1 促进葡萄糖代谢重编程
DOI：
10.18632/oncotarget.4508
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发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Ye L
中科院分区：
文献类型：
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作者：
Liu F;Zhang W;You X;Liu Y;Li Y;Wang Z;Wang Y;Zhang X;Ye L
葡萄糖代谢重编程是癌症的一个标志。肿瘤蛋白乙型肝炎x相互作用蛋白（HBXIP）在乳腺癌的发展中起作用。在本研究中，我们推测HBXIP可能参与了乳腺癌的糖代谢重编程。我们发现HBXIP导致细胞内葡萄糖和乳酸的生成增加，活性氧的生成减少。HBXIP抑制细胞色素c氧化酶2 （SCO2）和丙酮酸脱氢酶α 1 （PDHA1）合成的表达，这两个代谢因子是从氧化磷酸化到有氧糖酵解的转换。此外，miR-183/182和miR-96分别通过靶向其mRNA编码序列（CDSs）直接抑制SCO2和PDHA1的表达。有趣的是，HBXIP通过缺氧诱导因子1α (HIF1α)上调miR-183/96/182簇的表达。HBXIP通过von Hippel-Lindau蛋白（pVHL）与HIF1α的解耦作用增强了HIF1α的稳定性。此外，miR-183通过直接靶向VHL mRNA的CDS提高HIF1α蛋白水平，形成HIF1α/miR-183/pVHL/HIF1α的反馈回路。在功能上，hbxip升高的miR-183/96/182簇在体外增强了糖代谢重编程。hbxip触发的糖代谢重编程促进了体内乳腺癌的生长。因此，我们得出结论，癌蛋白HBXIP通过抑制乳腺癌中SCO2和PDHA1来增强糖代谢重编程。
The glucose metabolism reprogramming is a hallmark of cancer. The oncoprotein hepatitis B X-interacting protein (HBXIP) functions in the development of breast cancer. In this study, we supposed that HBXIP might be involved in the glucose metabolism reprogramming in breast cancer. We showed that HBXIP led to increases in generation of intracellular glucose and lactate, as well as decreases in generation of reactive oxygen species. Expression of synthesis of cytochrome c oxidase 2 (SCO2) and pyruvate dehydrogenase alpha 1 (PDHA1), two factors of metabolic switch from oxidative phosphorylation to aerobic glycolysis, was suppressed by HBXIP. In addition, miR-183/182 and miR-96 directly inhibited the expression of SCO2 and PDHA1 through targeting their mRNA coding sequences (CDSs), respectively. Interestingly, HBXIP elevated the miR-183/96/182 cluster expression through hypoxia-inducible factor 1α (HIF1α). The stability of HIF1α was enhanced by HBXIP through disassociating interaction of von Hippel-Lindau protein (pVHL) with HIF1α. Moreover, miR-183 increased the levels of HIF1α protein through directly targeting CDS of VHL mRNA, forming a feedback loop of HIF1α/miR-183/pVHL/HIF1α. In function, HBXIP-elevated miR-183/96/182 cluster enhanced the glucose metabolism reprogramming in vitro. HBXIP-triggered glucose metabolism reprogramming promoted the growth of breast cancer in vivo. Thus, we conclude that the oncoprotein HBXIP enhances glucose metabolism reprogramming through suppressing SCO2 and PDHA1 in breast cancer.