Research Papers:

The oncoprotein HBXIP promotes glucose metabolism reprogramming via downregulating SCO2 and PDHA1 in breast cancer

Fabao Liu, Weiying Zhang, Xiaona You, Yunxia Liu, Yinghui Li, Zhen Wang, Yue Wang, Xiaodong Zhang and Lihong Ye _

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Oncotarget. 2015; 6:27199-27213. https://doi.org/10.18632/oncotarget.4508

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Fabao Liu1,*, Weiying Zhang1,*, Xiaona You2, Yunxia Liu2, Yinghui Li1, Zhen Wang1, Yue Wang1, Xiaodong Zhang2,*, Lihong Ye1,*

1State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, P.R. China

2State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Lihong Ye, e-mail: [email protected]

Xiaodong Zhang, e-mail: [email protected]

Keywords: HBXIP, SCO2, PDHA1, glucose metabolism reprogramming, breast cancer

Received: January 27, 2015     Accepted: July 17, 2015     Published: July 30, 2015


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.

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