<p>PSAT1 Regulated Oxidation-Reduction Balance Affects the Growth and Prognosis of Epithelial Ovarian Cancer</p>

Abstract

Introduction: 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.

Cysteine-Rich Intestinal Protein 1 Served as an Epithelial Ovarian Cancer Marker via Promoting Wnt/β-Catenin-Mediated EMT and Tumour Metastasis

“…Ovarian cancer, a type of malignancy in the ovary, is the most lethal gynaecological carcinoma as well as the fifth leading cause of cancer mortality among women [ 1 ]. Over 85% of ovarian cancers originate from the epithelium (known as epithelial ovarian cancer, EOC), with serous ovarian cancer being the most common histological subtype [ 2 ]. Currently, the main treatment options for epithelial ovarian cancer are tumour cell reduction surgery and platinum-based chemotherapy, immunotherapy, and targeted therapy.…”

“…Currently, the main treatment options for epithelial ovarian cancer are tumour cell reduction surgery and platinum-based chemotherapy, immunotherapy, and targeted therapy. Although these therapeutic options are available, the overall five-year survival rate remains low, at around 30%-40% [ 2 ]. It is estimated that 22,530 patients were diagnosed with ovarian cancer in 2019 in the United States, of which 13,980 patients died [ 3 ].…”

Ferroptosis-Related Gene Signature: A New Method for Personalized Risk Assessment in Patients with Diffuse Large B-Cell Lymphoma

“… 31 PSAT1 is upregulated in Burkitt lymphoma via a MYC-dependent ATF4 transcription factor mechanism, and overexpression of PSAT1 is reportedly associated with poor prognoses in patients with Burkitt lymphoma, 32 nasopharyngeal carcinoma, 33 colorectal carcinoma, 34 , 35 and epithelial ovarian cancer. 36 Studies suggest that NGB may be a tumor suppressor that inhibits cell growth, cell aggregation, and tumorigenicity. 37 LAMP2 deficiency increases the risk of ferroptosis in retinal pigment epithelial cells.…”

Identification of Biomarkers Based on Bioinformatics Analysis: The Expression of Ubiquitin-Conjugating Enzyme E2T (UBE2T) in the Carcinogenesis and Progression of Hepatocellular Carcinoma

“…It has been reported that cytochrome CYP450 cyclooxygenase can catalyze the epoxidation of unsaturated fatty acids such as arachidonic acid and that arachidonic acid-derived products can effectively promote angiogenesis of lipids and tumor development [ 14 ]. Zhang et al reported that the growth and prognosis of cancer can be regulated by affecting the balance of redox reactions [ 15 ]. These findings support our enrichment analysis results.…”