Upregulation of Metallothionein 1 G (MT1G) Negatively Regulates Ferroptosis in Clear Cell Renal Cell Carcinoma by Reducing Glutathione Consumption DOI Creative Commons
Wu Zhang,

Min Luo,

Bingrui Xiong

et al.

Journal of Oncology, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 14

Published: Sept. 27, 2022

Ferroptosis is characterized by lipid peroxidation and iron accumulation, closely associated with clear cell renal carcinoma (ccRCC). It of great significance for prognostic prediction treatment ccRCC to find biomarkers related ferroptosis. We conducted several bioinformatic analyses using the transcriptome data clinical information derived from online databases. Firstly, we identified differentially expressed target genes in ccRCC. Then, t test COX analysis were used determine whether it was an independent factor combined information. String gene set enrichment (GSEA) predict its function. Finally, cells: 769-P KAKI-1 vitro verify regulation on proliferation apoptosis, metabolism, GSH which judge effect The study showed that MT1G downregulated tissues compared normal tissues. However, patients higher expression relatively had malignancy advanced stages. adverse prognosis protein interaction network GSEA metabolism-related proteins (GSR) oxidation-related (PLA2G2A). Samples high enriched “glutathione metabolism,” “oxidative phosphorylation,” “proteasome,” whose function involved metabolism peroxidation. term occurrence development tumors included “P53 signaling pathway.” Furthermore, experiments partially blocked ferroptosis induced erastin sorafenib-induced lines (769-P CAKI-1). mechanism may be affects regulating consumption cells. a negative regulator cells biomarker poor prognosis.

Language: Английский

Identification of a Novel Ferroptosis-Related Gene Prognostic Signature in Bladder Cancer DOI Creative Commons
Jiale Sun,

Wenchang Yue,

Jiawei You

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Sept. 7, 2021

Ferroptosis is a newly found non-apoptotic forms of cell death that plays an important role in tumors. However, the prognostic value ferroptosis-related genes (FRG) bladder cancer (BLCA) have not been well examined.FRG data and clinical information were collected from The Cancer Genome Atlas (TCGA). Then, significantly different FRGs investigated by functional enrichment analyses. FRG signature was identified univariate cox regression least absolute shrinkage selection operator (LASSO) analysis, which validated TCGA cohort Gene Expression Omnibus (GEO) cohort. Subsequently, nomogram integrating risk scores parameters established evaluated. Additionally, Set Enrichment Analyses (GSEA) performed to explore potential molecular mechanisms underlying our signature. Finally, expression three key verified specimens.Thirty-two TCGA-BLCA analyses showed these mainly related ferroptosis. Seven (TFRC, G6PD, SLC38A1, ZEB1, SCD, SRC, PRDX6) then develop Kaplan-Meier analysis confirmed predictive for overall survival (OS) both GEO A age demonstrated high accuracy, through calibration curves receiver operating characteristic (ROC) curve [area under (AUC) = 0.690]. GSEA alteration high- or low-risk group closely associated with experimental results PRDX6 BLCA.Herein, we novel maybe involved BLCA. It values predicting OS, targeting may be alternative BLCA treatment. Further studies are warranted uncover mediate progression.

Language: Английский

Citations

43
A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients DOI Creative Commons
Mei Chen, Zhenyu Nie, Yan Li

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Nov. 16, 2021

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

Language: Английский

Citations

43
Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis DOI Creative Commons
Li Li,

Minyan Wang,

Huabo Jiang

et al.

Asian Journal of Andrology, Journal Year: 2022, Volume and Issue: 25(3), P. 375 - 381

Published: Sept. 23, 2022

Bisphenol A is a common environmental factor and endocrine disruptor that exerts negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found ferroptosis phenomenon may exist. Mice were divided into six groups administered different doses via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine levels superoxide dismutase malondialdehyde. Epididymal sperm also semen analysis, tissue ferritin content determination, electron microscope observation mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, western blot analysis. Exposure decrease quality cause oxidative damage, iron accumulation, damage in testes mice. In addition, confirmed affect expression ferroptosis-related genes, glutathione peroxidase 4 (GPX4), heavy 1 (FTH1), cyclooxygenase 2 (COX2), acyl-CoA synthetase (ACSL4) tissues. Accordingly, speculate induces stress, which leads cells. Overall, inhibition be potential strategy reduce toxicity caused by A.

Language: Английский

Citations

32
Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma DOI Creative Commons
Jinyuan Shi, Pu Wu, Lei Sheng

et al.

Cancer Cell International, Journal Year: 2021, Volume and Issue: 21(1)

Published: Dec. 1, 2021

Papillary thyroid carcinoma (PTC) is the most common type of cancer (TC), accounting for more than 80% all cases. Ferroptosis a novel iron-dependent and Reactive oxygen species (ROS) reliant cell death which distinct from apoptosis, necroptosis pyroptosis. Considerable studies have demonstrated that ferroptosis involved in biological process various cancers. However, role PTC remains unclear. This study aims at exploring expression ferroptosis-related genes (FRG) their prognostic values PTC.

Language: Английский

Citations

41
Induction of ferroptosis promotes vascular smooth muscle cell phenotypic switching and aggravates neointimal hyperplasia in mice DOI Creative Commons

Shunchi Zhang,

Yanrou Bei,

Yueling Huang

et al.

Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(1)

Published: Oct. 3, 2022

Abstract Background Stent implantation-induced neointima formation is a dominant culprit in coronary artery disease treatment failure after percutaneous intervention. Ferroptosis, an iron-dependent regulated cell death, has been associated with various cardiovascular diseases. However, the effect of ferroptosis on remains unclear. Methods The mouse common right carotid arteries were ligated for 16 or 30 days, and tissues collected further analyses. Primary rat vascular smooth muscle cells (VSMCs) isolated from media aortas Sprague-Dawley (SD) rats used vitro culture experiments. Results Ferroptosis was positively formation. In vivo, RAS-selective lethal 3 (RSL3), activator, aggravated ligation-induced promoted VSMC phenotypic conversion. contrast, inhibitor, ferrostatin-1 (Fer-1), showed opposite effects mice. vitro, RSL3 switching contractile to synthetic phenotype, evidenced by increased markers (smooth myosin heavy chain calponin 1), decreased marker osteopontin. induction confirmed expression level ferroptosis-associated gene prostaglandin-endoperoxide synthase 2 ( Ptgs2 ). abolished Fer-1. Moreover, N -acetyl- l -cysteine (NAC), reactive oxygen species counteracted conversion VSMCs. Conclusions induces accelerates neointimal hyperplasia Our findings suggest inhibition as attractive strategy limiting restenosis.

Language: Английский

Citations

26
Identification and Validation in a Novel Quantification System of Ferroptosis Patterns for the Prediction of Prognosis and Immunotherapy Response in Left- and Right-Sided Colon Cancer DOI Creative Commons

Hengchun Zhang,

Shen-Hui Deng,

Ya-Nan Pi

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 4, 2022

Background This study aimed to establish a novel quantification system of ferroptosis patterns and comprehensively analyze the relationship between score (FS) immune cell infiltration (ICI) characterization, tumor mutation burden (TMB), prognosis, therapeutic sensitivity in left-sided right-sided colon cancers (LCCs RCCs, respectively). Methods We evaluated 444 LCCs RCCs based on 59 ferroptosis-related genes (FRGs). The FS was constructed quantify by using principal component analysis algorithms. Next, prognostic value sensitivities were multiple methods. Finally, we performed weighted gene co-expression network (WGCNA) identify key FRGs. IMvigor210 cohort, TCGA-COAD proteomics Immunophenoscores used verify predictive abilities Results Two clusters determined. Ferroptosis cluster B demonstrated high degree congenital ICI stromal-related signal enrichment with poor prognosis. response targeted inhibitors, immunotherapy significantly different low groups (HSG LSG, HSG characterized TMB microsatellite instability-high subtype Meanwhile, LSG more likely benefit from immunotherapy. ALOX5 identified as FRG FS. Patients protein levels had poorer prognoses. Conclusion work revealed that evaluation subtypes will contribute gaining insight into heterogeneity RCCs. for played non-negligible role predicting individualized strategies.

Language: Английский

Citations

25
Nuclear localization of STING1 competes with canonical signaling to activate AHR for commensal and intestinal homeostasis DOI Creative Commons
Ruoxi Zhang, Chunhua Yu, Herbert J. Zeh

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(12), P. 2736 - 2754.e8

Published: Nov. 27, 2023

Language: Английский

Citations

15
Glycyrrhizic acid protects against temporal lobe epilepsy in young rats by regulating neuronal ferroptosis through the miR‐194‐5p/PTGS2 axis DOI Creative Commons

Tingting Yi,

Li‐Mei Zhang,

Xiang-nan Huang

et al.

The Kaohsiung Journal of Medical Sciences, Journal Year: 2023, Volume and Issue: 39(2), P. 154 - 165

Published: Jan. 17, 2023

Abstract Temporal lobe epilepsy (TLE) leads to extensive degradation of the quality life patients. Glycyrrhizic acid (GA) has been reported exert neuroprotective effects on status epilepticus. Herein, current study set out explore functional mechanism GA in TLE young rats. Firstly, rat models were established using lithium chloride and pilocarpine regimen then subjected treatment with different doses GA, miR‐194‐5p‐antagomir, or/and sh‐prostaglandin‐endoperoxide synthase 2 (PTGS2) observe changes iron content, glutathione malondialdehyde levels, GPX4 (glutathione peroxidase 4) PTGS2 protein levels hippocampus. Neuronal injury apoptosis assessed through HE, Nissl, TUNEL staining. Additionally, expression patterns miR‐194‐5p detected. The binding site was verified a dual‐luciferase assay. Briefly, (20, 40, 60 mg/kg) reduced epileptic score, frequency, duration rats, along reductions lipid peroxidation, neuronal injury, Silencing partly annulled action inhibiting ferroptosis attenuating validated as target miR‐194‐5p. inhibited ameliorated rats via miR‐194‐5p/PTGS2 axis. Overall, our findings indicated that exerts protective against by

Language: Английский

Citations

14
Bioinformatics analysis of genes related to iron death in diabetic nephropathy through network and pathway levels based approaches DOI Creative Commons
Yaling Hu, Shuang Liu, Wenyuan Liu

et al.

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(11), P. e0259436 - e0259436

Published: Nov. 4, 2021

Diabetic nephropathy is one of the common microvascular complications diabetes. Iron death a recently reported way cell death. To explore effects iron on diabetic nephropathy, score was analyzed based network and pathway levels. Furthermore, markers related to were screened. Using RNA-seq data samples clustered uniformly disease classified. Differentially expressed gene analysis conducted typed samples, WGCNA algorithm used obtain key modules. String database perform protein interaction module genes for selection Hub genes. Moreover, principal component method applied get transcription factors non-coding genes, which interact with gene. All can be divided into two categories shows that are significantly different. (FPR3, C3AR1, CD14, ITGB2, RAC2 ITGAM) in obtained through expression differential between different subtypes. Non-coding including hsa-miR-572, hsa-miR-29a-3p, hsa-miR-29b-3p, hsa-miR-208a-3p, hsa-miR-153-3p hsa-miR-29c-3p, may nephropathy. Transcription HIF1α, KLF4, KLF5, RUNX1, SP1, VDR WT1 The above collectively involved occurrence development further studied future. these potential target therapeutic drugs.

Language: Английский

Citations

33
Ferroptosis-Related Gene MT1G as a Novel Biomarker Correlated With Prognosis and Immune Infiltration in Colorectal Cancer DOI Creative Commons
Bi Peng, Jinwu Peng,

Fanhua Kang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 20, 2022

Ferroptosis, a newly discovered way of cell death, has been proved to be involved in the oncogenesis and development cancers, including colorectal cancer (CRC). Here, by identifying differentially expressed genes (DEGs) from three CRC transcriptome microarray datasets (GSE20842, GSE23878, GSE25070), we found that expression MT1G was significantly decreased tissues, patients with high level displayed poor prognosis. Quantitative PCR (qPCR) further confirmed downregulated two cells, HCT8 HCT116. The colony-forming assay indicated overexpression exhibited remarkable inhibition proliferation HCT116 cells. In addition, explored co-expressed gain better understanding its potential signaling pathways. Aberrantly also affected immune response patients. Collectively, these findings might deepen our comprehension on biological implications CRC.

Language: Английский

Citations

22