Silencing of PTPN18 Induced Ferroptosis in Endometrial Cancer Cells Through p-P38-Mediated GPX4/xCT Down-Regulation

Wang, Haibo; Peng, Siyuan; Cai, Junhong; Bao, Shaowen

doi:10.2147/cmar.s278728

Cited by 27 publications

(25 citation statements)

References 29 publications

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“…miR-324-3p reverses cisplatin resistance by inducing GPX4-mediated ferroptosis in lung adenocarcinoma ( Deng et al, 2021 ). SUV39H1 deficiency inhibits the growth of clear cell renal cell carcinoma by inducing ferroptosis ( Wang et al, 2021 ). Silencing PTPN18 can induce ferroptosis in endometrial cancer through p-P38-mediated downregulation of GPX4/xCT ( Wang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients

Chen

Nie

et al. 2021

Front. Cell Dev. Biol.

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Background: Ferroptosis is closely related to the occurrence and development of cancer. An increasing number of studies have induced ferroptosis as a treatment strategy for cancer. However, the predictive value of ferroptosis-related lncRNAs in bladder cancer (BC) still need to be further elucidated. The purpose of this study was to construct a predictive signature based on ferroptosis-related long noncoding RNAs (lncRNAs) to predict the prognosis of BC patients.Methods: We downloaded RNA-seq data and the corresponding clinical and prognostic data from The Cancer Genome Atlas (TCGA) database and performed univariate and multivariate Cox regression analyses to obtain ferroptosis-related lncRNAs to construct a predictive signature. The Kaplan-Meier method was used to analyze the overall survival (OS) rate of the high-risk and low-risk groups. Gene set enrichment analysis (GSEA) was performed to explore the functional differences between the high- and low-risk groups. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between the predictive signature and immune status. Finally, the correlation between the predictive signature and the treatment response of BC patients was analyzed.Results: We constructed a signature composed of nine ferroptosis-related lncRNAs (AL031775.1, AL162586.1, AC034236.2, LINC01004, OCIAD1-AS1, AL136084.3, AP003352.1, Z84484.1, AC022150.2). Compared with the low-risk group, the high-risk group had a worse prognosis. The ferroptosis-related lncRNA signature could independently predict the prognosis of patients with BC. Compared with clinicopathological variables, the ferroptosis-related lncRNA signature has a higher diagnostic efficiency, and the area under the receiver operating characteristic curve was 0.707. When patients were stratified according to different clinicopathological variables, the OS of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the high-risk group. ssGSEA showed that the predictive signature was significantly related to the immune status of BC patients. High-risk patients were more sensitive to anti-PD-1/L1 immunotherapy and the conventional chemotherapy drugs sunitinib, paclitaxel, cisplatin, and docetaxel.Conclusion: The predictive signature can independently predict the prognosis of BC patients, provides a basis for the mechanism of ferroptosis-related lncRNAs in BC and provides clinical treatment guidance for patients with BC.

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Section: Introductionmentioning

confidence: 99%

A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients

Chen

Nie

et al. 2021

Front. Cell Dev. Biol.

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“…Inhibiting GPX4 by resibufogenin (RB) induced ferroptotic cancer cell death and suppressed tumor growth in vivo ( Shen et al, 2021 ). GPX4 was reported to be involved in the metformin, miR-324-3p, and loss of PTPN18 or SRSF9 induced ferroptosis ( Deng et al, 2021 ; Hou et al, 2021 ; Wang et al, 2021b , c ). Apoptosis inducing factor mitochondria associated 2 (AIFM2, also known as PRG3 or FSP1), a traditional apoptotic regulator, was identified as a new ferroptosis regulator and found to block the RSL3-, sorafenib-, and erastin-induced ferroptosis of cancer cells, and inhibition of AIFM2-dependent pathway enhanced the antitumor activity of sorafenib in mouse model ( Bersuker et al, 2019 ; Doll et al, 2019 ; Dai et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Immunological Role of Key Genes of Ferroptosis in Pan-Cancer

Shi

Hao

Fan

et al. 2021

Front. Cell Dev. Biol.

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Solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and apoptosis inducing factor mitochondria associated 2 (AIFM2) are the key regulators in ferroptosis. However, the expression patterns and prognostic roles of these genes in pan-cancer are still largely unclear. The expression patterns and prognostic roles of SLC7A11, GPX4, and AIFM2 and the relationships between the expression levels of these genes and immune infiltration levels in pan-cancer were analyzed by using TIMER, gene expression profiling interactive analysis (GEPIA), Oncomine, and Kaplan–Meier databases. Our results showed that both SLC7A11 and GPX4 were overexpressed in colorectal cancer, and SLC7A11 was overexpressed in lung cancer. High levels of SLC7A11 and AIFM2 were significantly linked with the shortened disease-free survival and overall survival (OS) in adrenocortical carcinoma (ACC), respectively. And high expression of SLC7A11, GPX4, and AIFM2 were significantly correlated with the shortened OS of acute myeloid leukemia patients. In esophageal carcinoma (ESCA), GPX4 expression was significantly associated with the infiltration of macrophage and myeloid dendritic cell, and AIFM2 expression was significantly associated with the infiltration of CD4+ T cell. Importantly, GPX4 expression was positively correlated with the expression levels of monocyte markers (CD14 and CD115) and M2 macrophage markers (VSIG4 and MS4A4A) both in ESCA and in head and neck squamous cell carcinoma (HNSC). In summary, SLC7A11, GPX4, and AIFM2 are dysregulated in many types of cancers, and are candidate prognostic biomarkers for many types of cancers, and can be used to evaluate the infiltration of immune cells in tumor tissues.

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“…xCT is composed of cystine/glutamate transporters, and it mainly provides a substrate for glutathione synthesis ( 10 ). The inhibition of xCT would decrease the capacity of GPX4 to clear lipid ROS via inadequate glutathione synthesis and finally induce cell death ( 10 , 26 ). According to results of the present study, OP-B suppressed the expression of GPX4 and xCT, suggesting that OP-B-induced ferroptotic cell death may be achieved by inhibiting the GPX4/xCT system.…”

Section: Discussionmentioning

confidence: 99%

Ophiopogonin B induces gastric cancer cell death by blocking the GPX4/xCT‑dependent ferroptosis pathway

Zhang

et al. 2022

Oncol Lett

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Ophiopogonin B (OP-B) is extensively applied as a treatment for pulmonary disease and is reported to suppress lung cancer. However, further study is needed to determine whether OP-B suppresses gastric cancer (GC). The mRNA levels of prostaglandin-endoperoxide synthase 2 (Ptgs2) and ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (Chac1) were determined using quantitative PCR. Ptgs2 and Chac1 mRNA levels were significantly increased in GC cancer tissues compared with those of adjacent normal controls. The CCK-8 assay revealed that OP-B suppressed GC cell viability in a time- and dose-dependent manner. The administration of OP-B in combination with different cell death inhibitors showed that only the ferroptosis inhibitor, ferrostatin-1 (Fer-1), abolished the OP-B-induced death of both AGS and NCI-N87 cells, but not other inhibitors. Western blot analysis indicated that OP-B reduced the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11, xCT) but had no effects on the expression of nuclear receptor coactivator 4 (NCOA4) and ferritin heavy chain 1 (FTH1) in AGS and NCI-N87 cells. In vivo administration of OP-B reduced the volume and weight of AGS tumors. In addition, the expression of GPX4 and xCT was reduced in nude mice treated with OP-B compared with control mice. In summary, results of the present study suggest that OP-B induces ferroptosis in gastric cancer cells by blocking the GPX4/xCT system.

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Silencing of PTPN18 Induced Ferroptosis in Endometrial Cancer Cells Through p-P38-Mediated GPX4/xCT Down-Regulation

Cited by 27 publications

References 29 publications

A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients

A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients

Prognostic and Immunological Role of Key Genes of Ferroptosis in Pan-Cancer

Ophiopogonin B induces gastric cancer cell death by blocking the GPX4/xCT‑dependent ferroptosis pathway

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