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

Oncotarget. 2017 Sep 19;8(60):101309-101324. doi: 10.18632/oncotarget.21087. eCollection 2017 Nov 24.

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.

Keywords: biomarker; cell proliferation; meta-analysis; prognostic significance; survival.