Identification and validation of PSAT1 as a potential prognostic factor for predicting clinical outcomes in patients with colorectal carcinoma

Qian, Cheng; Xia, Yongsheng; Ren, Yun; Yin, Yanbin; Deng, Anmei

doi:10.3892/ol.2017.7211

Cited by 25 publications

(24 citation statements)

References 23 publications

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“…It is reported that PSAT1 expression was remarkably heightened in non-small cell lung cancer (NSCLC) and forecasted poor clinical outcome of NSCLC patients [ 27 ]. Furthermore, PSAT1 is considered as the highest upregulated gene in CRC tumors as well as highly expressed in chemoresistant disease patients [ 28 ]. It has been manifested that GSK3β activity was elevated in cancerous tissues [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway

et al. 2020

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It is unclear about the functional role of microRNA-133a-3p (miR-133a-3p) in intracranial aneurysm (IA). Hence, the aim of the present study was to investigate the regulatory role of miR-133a-3p on the regulation of vascular endothelial injury-induced IA through phosphoserine aminotransferase 1 (PSAT1)/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway. Normal intracranial arteriole tissues and IA tissues were gathered from patients with brain trauma and IA. The expression of miR-133a-3p, PSAT1, GSK3β, and β-catenin in tissues was determined by RT-qPCR and western blot analysis. The endothelial cells (ECs) of the human IA were cultured and treated with miR-133a-3p mimic and si-PSAT1 to determine their functions in endothelial cell migration, apoptosis, and proliferation. The expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, Ki-67, CyclinD1, Bax, and Bcl-2 in ECs were tested by RT-qPCR or western blot analysis. Moreover, IA rat model was established to detect the pathological changes and the expression of miR-133a-3p, PSAT1, GSK3β, β-catenin, VEGF, and MMP-9 in IA tissues in vivo. Expression of miR-133a-3p was related to the number and size of IA. MiR-133a-3p expression was deceased and the PSAT1, GSK3β, and β-catenin expression was raised in IA. Restored miR-133a-3p and depleted PSAT1 alleviated the pathological change; reduced PSAT1, GSK3β, and β-catenin expression in IA; suppressed apoptosis and advanced proliferation and migration of IA ECs, as well as reduced VEGF and MMP-9 expression in IA tissues in vivo. Our study suggests that overexpression of miR-133a-3p or downregulation of PSAT1 restrains endothelial cell damage and advances endothelial cell proliferation via inhibiting the GSK3β/β-catenin pathway in IA. MiR-133a-3p might be a potential candidate marker and therapeutic target for IA.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway

et al. 2020

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“…Several studies have shown that high PSAT1 expression is implicated in malignant metastasis, chemosensitivity, and poor outcomes. 6,7,17 Inhibiting PSAT1 has been found to enhance the sensitivity of non-small cell lung cancer cells in the absence of glutamine. 18 Dai et al found that silencing PSAT1 reduced angiogenesis and cisplatin resistance via GSK3β/β-catenin pathway.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang¹,

Li²,

Dong³

et al. 2020

OTT

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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.

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“…The latter product is finally converted by phosphoserine phosphatase (PSPH) into serine. Overexpression of PHGDH and PSAT1 due to structural alterations or functional mechanisms was found in many types of cancers [15][16][17][18]. Importantly, some of these tumors are sensitive to targeted SBP inhibition [19,20].…”

Section: Introductionmentioning

confidence: 99%

Serine Biosynthesis Pathway Supports MYC–miR-494–EZH2 Feed-Forward Circuit Necessary to Maintain Metabolic and Epigenetic Reprogramming of Burkitt Lymphoma Cells

Białopiotrowicz

Noyszewska‐Kania

Kachamakova‐Trojanowska

et al. 2020

Cancers

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Burkitt lymphoma (BL) is a rapidly growing tumor, characterized by high anabolic requirements. The MYC oncogene plays a central role in the pathogenesis of this malignancy, controlling genes involved in apoptosis, proliferation, and cellular metabolism. Serine biosynthesis pathway (SBP) couples glycolysis to folate and methionine cycles, supporting biosynthesis of certain amino acids, nucleotides, glutathione, and a methyl group donor, S-adenosylmethionine (SAM). We report that BLs overexpress SBP enzymes, phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1). Both genes are controlled by the MYC-dependent ATF4 transcription factor. Genetic ablation of PHGDH/PSAT1 or chemical PHGDH inhibition with NCT-503 decreased BL cell lines proliferation and clonogenicity. NCT-503 reduced glutathione level, increased reactive oxygen species abundance, and induced apoptosis. Consistent with the role of SAM as a methyl donor, NCT-503 decreased DNA and histone methylation, and led to the re-expression of ID4, KLF4, CDKN2B and TXNIP tumor suppressors. High H3K27me3 level is known to repress the MYC negative regulator miR-494. NCT-503 decreased H3K27me3 abundance, increased the miR-494 level, and reduced the expression of MYC and MYC-dependent histone methyltransferase, EZH2. Surprisingly, chemical/genetic disruption of SBP did not delay BL and breast cancer xenografts growth, suggesting the existence of mechanisms compensating the PHGDH/PSAT1 absence in vivo.

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Identification and validation of PSAT1 as a potential prognostic factor for predicting clinical outcomes in patients with colorectal carcinoma

Cited by 25 publications

References 23 publications

RETRACTED ARTICLE: Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway

RETRACTED ARTICLE: Restored microRNA-133a-3p or Depleted PSAT1 Restrains Endothelial Cell Damage-Induced Intracranial Aneurysm Via Suppressing the GSK3β/β-Catenin Pathway

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

Serine Biosynthesis Pathway Supports MYC–miR-494–EZH2 Feed-Forward Circuit Necessary to Maintain Metabolic and Epigenetic Reprogramming of Burkitt Lymphoma Cells

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