OncoTargets and Therapy (2020-06-01)

PSAT1 Regulated Oxidation-Reduction Balance Affects the Growth and Prognosis of Epithelial Ovarian Cancer

  • Zhang Y,
  • Li J,
  • Dong X,
  • Meng D,
  • Zhi X,
  • Yuan L,
  • Yao L

Journal volume & issue
Vol. Volume 13
pp. 5443 – 5453

Abstract

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Yiqun Zhang,1– 3,* Jiajia Li,1– 3,* Xuhui Dong,1– 3 Dan Meng,4 Xiuling Zhi,4 Lei Yuan,1– 3 Liangqing Yao1– 3 1Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, People’s Republic of China; 4Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Yuan; Liangqing YaoDepartment of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, People’s Republic of ChinaTel +86-18964075180Email [email protected]; [email protected]: A growing number of studies have found that the serine-glycine biosynthesis pathway is highly activated for biosynthesis in cancer progression and metastasis. Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second step of the serine-glycine biosynthesis pathway; the effects and mechanism of PSAT1 in epithelial ovarian cancer (EOC) remains unclear.Materials and Methods: The expression of PSAT1 in clinical EOC samples and normal ovarian tissues was conducted by RT-PCR, Western blot, and immunohistochemical staining. Survival analysis of PSAT1 in ovarian cancer was performed by using the public database. Following the downregulation of PSAT1, the cell growth, cell apoptosis, and cell cycle in ovarian cancer cells were respectively examined by the soft agar colony formation assay and flow cytometry analysis. Then the glutathione (GSH) levels, the GSH/GSSG ratio, the NADPH/NADP ratio, and the cellular reactive oxygen species (ROS) levels were tested to analyze the oxidation-reduction balance in PSAT1-depleted ovarian cancer cells.Results: PSAT1 is markedly over-expressed in clinical EOC samples (n = 90) compared to that in normal ovarian tissues (n = 10), and the expression of PSAT1 is correlated with histological subtype, FIGO stage, histological grade, lymph node metastasis, distant metastasis and the presence of ascites. Public database analysis shows that higher PSAT1 indicates poor survival in EOC patients. Downregulation of PSAT1 in EOC cells inhibits growth, induces apoptosis and cell cycle arrest in vitro. EOC cells with high PSAT1 levels have increased a higher GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio and lower reactive oxygen species (ROS) content. The cancer-killing effects of PSAT1 knockdown are reversed by exogenous glutathione. PSAT1 participates in cancer growth by regulating oxidation-reduction balance.Conclusion: Therefore, these results highlight the potential of PSAT1 inhibitors or metabolic substrate deprivation as therapeutic strategies for treating patients with EOC, especially those with advanced stages of cancer.Keywords: phosphoserine aminotransferase 1, oxidative stress, serine-glycine biosynthesis pathway, epithelial ovarian cancer

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