GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers

Hu, Qingyi; Chen, Jiaoshun; Yang, Wen Bin; Xu, Ming; Zhou, Jun; Tan, Jie; Huang, Tao

doi:10.3389/fonc.2023.990551

Cited by 10 publications

(11 citation statements)

References 89 publications

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“…Emerging evidence has suggested that GPX3 has a diverse role in different types of human cancers, serving as a pro-survival protein in myeloid leukemia and clear cell renal cell carcinoma, and as a tumor suppressor in lung, ovarian and gastric cancer ( 10-14 ). Consistently, a previous study demonstrated that GPX3 was downregulated in human cancers, but it was positively associated with poor outcomes ( 15 ), thus supporting the controversial role of GPX3 in cancer. It has been also reported that GPX3 is highly involved in cancer metastasis and chemotherapy resistance ( 15 ).…”

Section: Introductionsupporting

confidence: 83%

“…Consistently, a previous study demonstrated that GPX3 was downregulated in human cancers, but it was positively associated with poor outcomes ( 15 ), thus supporting the controversial role of GPX3 in cancer. It has been also reported that GPX3 is highly involved in cancer metastasis and chemotherapy resistance ( 15 ). Nevertheless, the particular role of GPX3 in PC has not been extensively investigated.…”

Section: Introductionsupporting

confidence: 83%

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GPX3 represses pancreatic cancer cell proliferation, migration and invasion, and improves their chemo‑sensitivity by regulating the JNK/c‑Jun signaling pathway

Ma,

Zhang,

Gao

et al. 2024

Exp Ther Med

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Pancreatic cancer (PC) is a deadly and aggressive disease, which is characterized by poor prognosis. It has been reported that glutathione peroxidase 3 (GPX3) is involved in the development of several types of cancer. The present study aimed to explore the regulatory role of GPX3 in PC and uncover its underlying mechanism. Bioinformatics analysis was initially carried out to predict the expression profile of GPX3 in PC and its association with prognosis. The expression levels of GPX3 were also detected in PC cells by reverse transcription-quantitative PCR and western blot analysis. Following transfection to induce GPX3 overexpression, the proliferation ability of PC cells was assessed by Cell Counting Kit-8, colony formation and 5-ethynyl-2'-deoxyuridine incorporation assays. In addition, wound healing and Transwell assays were performed to evaluate the migration and invasion abilities of PC cells. Cell apoptosis was assessed by flow cytometric analysis. The expression levels of epithelial-mesenchymal transition (EMT)-, apoptosis-, and JNK signaling-related proteins were detected by western blot analysis. Additionally, for rescue experiments, JNK signaling was activated following cell treatment with anisomycin. The results showed that GPX3 was downregulated in PC and its expression was associated with favorable prognosis. In addition, cell transfection-induced GPX3 overexpression markedly inhibited cell proliferation, migration and invasion, and inhibited EMT. In addition, GPX3 improved the chemo-sensitivity of PC and gemcitabine (GEM)-resistant PC cells to GEM. Furthermore, GPX3 significantly suppressed JNK/c-Jun signaling in PC, while anisomycin treatment reversed the inhibitory effects of GPX3 on the malignant behavior and chemo-resistance of PC cells. The results of the present study indicated that GPX3 could serve as a tumor suppressor in PC via inhibiting JNK/c-Jun signaling, thus providing novel insights into the treatment of PC.

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Section: Introductionsupporting

confidence: 83%

Section: Introductionsupporting

confidence: 83%

GPX3 represses pancreatic cancer cell proliferation, migration and invasion, and improves their chemo‑sensitivity by regulating the JNK/c‑Jun signaling pathway

Ma,

Zhang,

Gao

et al. 2024

Exp Ther Med

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“…It appears that DNMT1 has the strongest positive correlation with pyrimidine metabolism in STAD patients ( R = 0.50, P < 0.01) and GPX3 has the strongest negative correlation ( R = −0.48, P < 0.01; Figure 5(f) ). Hu et al [ 28 ] showed a link between the expression level of GPX3 and resistance to a chemotherapeutic drug, 5-fluorouracil (5-Fu), which can affect pyrimidine metabolism [ 29 ]. Therefore, we chose GPX3 as the target of interest for conducting further validation experiments.…”

Section: Resultsmentioning

confidence: 99%

“…Afects 5-Fu Resistance. Hu et al [28] found an association between GPX3 and drug sensitivity to the antitumor drug, 5-Fu. Moreover, our experimental results demonstrated that GPX3 may afect 5-Fu resistance in STAD by afecting the expression of CAD and inhibiting the level of pyrimidine metabolism.…”

Section: Exploration Of the Mechanism By Which Gpx3mentioning

confidence: 99%

GPX3-Mediated Oxidative Stress Affects Pyrimidine Metabolism Levels in Stomach Adenocarcinoma via the AMPK/mTOR Pathway

Zhang,

Yang,

Kuang

et al. 2024

International Journal of Clinical Practice

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Background. Amino acid metabolism, including ATP production, nucleotide synthesis, and redox homeostatic processes, are associated with proliferation and differentiation of tumor cells. This study aimed to identify novel prognostic biomarkers and potential therapeutic targets of amino acid metabolism-related genes for stomach adenocarcinoma (STAD). Methods. RNA sequencing transcriptome data in the TCGA-STAD (training set) and GTEx datasets (validation set) were used. The LIMMA R program enabled the differentially expressed amino acid metabolism-related genes (AAMRGs) to be found. A prognostic risk score model based on clinical phenotypic features was built using LASSO regression and step multi-Cox analyses. Gene set enrichment analysis (GSEA) was used to find potential molecular pathways associated with STAD. Hierarchical cluster analysis was used to evaluate pyrimidine metabolism. Cultured STAD cells assessed the proliferation of STAD and upregulation of GPX3 expression by CCK8 and flow cytometry. Transwell and wound healing assays assessed the impact of GPX3 on invasion and migration of STAD cells. Western blot and qRT-PCR were used to measure changes in pyrimidine metabolism-related markers and active molecules involved in the AMPK/mTOR signaling pathway. Results. Three AAMRGs, DNMT1, F2R, and GPX3, could independently predict the course of STAD. Pyrimidine metabolism appeared to be significantly associated with these by GSEA and clustering analyses. Pyrimidine metabolism was negatively correlated with GPX3. Functional studies using an overexpressed GPX3 plasmid showed an enhanced migration and invasion of STAD cells as well as the expression of genes associated with pyrimidine metabolism and the AMPK/mTOR signaling pathway. By using a CAD siRNA, it was found that that GPX3 affected 5-fluorouracil resistance during de novo synthesis of pyrimidine through the CAD-UMPS signaling axis. Conclusions. GPX3 which regulates the level of pyrimidine metabolism through the AMPK/mTOR pathway was found to be closely associated with STAD. Our findings demonstrate GPX3 is a reliable biomarker for the prognosis of amino acid metabolism and a probable target for STAD therapy.

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“…These findings suggest that GPX3 and the JNK pathway could serve as potential therapeutic targets for non-small cell lung cancer (5). GPX3 can inhibit the migration and invasion of gastric cancer cells and selectively inhibit the NF-κB/Wnt5a/JNK signaling pathway (42).…”

Section: Gpx3mentioning

confidence: 99%

Advances in the role of GPX3 in ovarian cancer (Review)

Geng,

Zhou,

Wang

2024

Int J Oncol

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Ovarian cancer (OC) is the 5th most common malignancy in women, and the leading cause of death from gynecologic malignancies. Owing to tumor heterogeneity, lack of reliable early diagnostic methods and high incidence of chemotherapy resistance, the 5-year survival rate of patients with advanced OC remains low despite considerable advances in detection and therapeutic approaches. Therefore, identifying novel therapeutic targets to improve the prognosis of patients with OC is crucial. The expression of glutathione peroxidase 3 (GPX3) plays a crucial role in the growth, proliferation and differentiation of various malignant tumors. In OC, GPX3 is the only antioxidant enzyme the high expression of which is negatively correlated with the overall survival of patients. GPX3 may affect lipid metabolism in tumor stem cells by influencing redox homeostasis in the tumor microenvironment. The maintenance of stemness in OC stem cells (OCSCs) is strongly associated with poor prognosis and recurrence in patients. The aim of the present study was to review the role of GPX3 in OC and investigate the potential factors and effects of GPX3 on OCSCs. The findings of the current study offer novel potential targets for drug therapy in OC, enhance the theoretical foundation of OC drug therapy and provide valuable references for clinical treatment. Contents 1. Introduction 2. GPX3 3. OC and OCSCs 4. Association of GPX3 with OC 5. Conclusion and prospects

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GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers

Cited by 10 publications

References 89 publications

GPX3 represses pancreatic cancer cell proliferation, migration and invasion, and improves their chemo‑sensitivity by regulating the JNK/c‑Jun signaling pathway

GPX3 represses pancreatic cancer cell proliferation, migration and invasion, and improves their chemo‑sensitivity by regulating the JNK/c‑Jun signaling pathway

GPX3-Mediated Oxidative Stress Affects Pyrimidine Metabolism Levels in Stomach Adenocarcinoma via the AMPK/mTOR Pathway

Advances in the role of GPX3 in ovarian cancer (Review)

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