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Identification of glycerol-3-phosphate dehydrogenase 1 as a tumour suppressor in human breast cancer

2017; Impact Journals LLC; Volume: 8; Issue: 60 Linguagem: Inglês

10.18632/oncotarget.21087

1949-2553

Cefan Zhou, Jing Yu, Ming Wang, Jing Yang, Hui Xiong, Huang Huang, Dongli Wu, Shimeng Hu, Yefu Wang, Xing‐Zhen Chen, Jingfeng Tang,

Cancer, Lipids, and Metabolism

// Cefan Zhou 1, 2 , Jing Yu 2, 3 , Ming Wang 4 , Jing Yang 5 , Hui Xiong 6 , Huang Huang 1 , Dongli Wu 2 , Shimeng Hu 2 , Yefu Wang 2 , Xing-Zhen Chen 1, 7 and Jingfeng Tang 1 1 Institute of Biomedical and Pharmaceutical Sciences, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, Hubei, China 2 The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China 3 Department of Clinical Laboratory, Hubei Cancer Hospital, Wuhan, Hubei, China 4 Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China 5 Institute for Immunology, Tsinghua University, Beijing, China 6 XiLi People's Hospital, Shenzhen, Guangdong, China 7 Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada Correspondence to: Jingfeng Tang, email: Jingfeng_HUT@163.com Keywords: prognostic significance, biomarker, cell proliferation, survival, meta-analysis Received: July 05, 2017 Accepted: August 27, 2017 Published: September 19, 2017 ABSTRACT In the present study, we found the mRNA expression level of glycerol-3-phosphate dehydrogenase (GPD1) was significantly downregulated in human breast cancer patients. Patients with reduced GPD1 expression exhibited poorer overall metastatic relapse-free survival ( p = 0.0013). Further Cox proportional hazard model analysis revealed that the reduced expression of GPD1 is an independent predictor of overall survival in oestrogen receptor-positive ( p = 0.0027, HR = 0.91, 95% CI = 0.85–0.97, N = 3,917) and nodal-negative ( p = 0.0013, HR = 0.87, 95% CI = 0.80–0.95, N = 2,456) breast cancer patients. We also demonstrated that GPD1 was a direct target of miR-370, which was significantly upregulated in human breast cancer. We further showed that exogenous expression of GPD1 in human MCF-7 and MDA-MB-231 breast cancer cells significantly inhibited cell proliferation, migration, and invasion. Our results, therefore, suggest a novel tumour suppressor function for GPD1 and contribute to the understanding of cancer metabolism.