鉴定甘油-3-磷酸脱氢酶1作为人类乳腺癌中的一种肿瘤抑制因子。
Identification of glycerol-3-phosphate dehydrogenase 1 as a tumour suppressor in human breast cancer.
作者信息
Zhou Cefan, Yu Jing, Wang Ming, Yang Jing, Xiong Hui, Huang Huang, Wu Dongli, Hu Shimeng, Wang Yefu, Chen Xing-Zhen, Tang Jingfeng
机构信息
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.
The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
出版信息
Oncotarget. 2017 Sep 19;8(60):101309-101324. doi: 10.18632/oncotarget.21087. eCollection 2017 Nov 24.
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 ( = 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 ( = 0.0027, HR = 0.91, 95% CI = 0.85-0.97, = 3,917) and nodal-negative ( = 0.0013, HR = 0.87, 95% CI = 0.80-0.95, = 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.
在本研究中，我们发现甘油-3-磷酸脱氢酶（GPD1）的mRNA表达水平在人类乳腺癌患者中显著下调。GPD1表达降低的患者表现出较差的总体无转移复发生存率（P = 0.0013）。进一步的Cox比例风险模型分析显示，GPD1表达降低是雌激素受体阳性（P = 0.0027，HR = 0.91，95% CI = 0.85 - 0.97，n = 3917）和淋巴结阴性（P = 0.0013，HR = 0.87，95% CI = 0.80 - 0.95，n = 2456）乳腺癌患者总体生存的独立预测因素。我们还证明GPD1是miR - 370的直接靶点，miR - 370在人类乳腺癌中显著上调。我们进一步表明，在人MCF - 7和MDA - MB - 231乳腺癌细胞中外源表达GPD1可显著抑制细胞增殖、迁移和侵袭。因此，我们的结果提示GPD1具有新的肿瘤抑制功能，并有助于对癌症代谢的理解。
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