Identification of glycerol-3-phosphate dehydrogenase 1 as a tumour suppressor in human breast cancer
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Cefan Zhou1,2, Jing Yu2,3, Ming Wang4, Jing Yang5, Hui Xiong6, Huang Huang1, Dongli Wu2, Shimeng Hu2, Yefu Wang2, Xing-Zhen Chen1,7 and Jingfeng Tang1
1Institute 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
2The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China
3Department of Clinical Laboratory, Hubei Cancer Hospital, Wuhan, Hubei, China
4Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
5Institute for Immunology, Tsinghua University, Beijing, China
6XiLi People's Hospital, Shenzhen, Guangdong, China
7Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
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
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.
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