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Comprehensive analysis of ferroptosis-related genes indicates that TRIM46 is a novel biomarker and promotes the progression of ovarian cancer via modulating ferroptosis and Wnt signaling pathway.对铁死亡相关基因的综合分析表明,TRIM46是一种新型生物标志物,通过调节铁死亡和Wnt信号通路促进卵巢癌的进展。
Am J Cancer Res. 2024 Oct 15;14(10):4686-4707. doi: 10.62347/ONUY8904. eCollection 2024.
2
A Novel Defined Risk Signature of the Ferroptosis-Related Genes for Predicting the Prognosis of Ovarian Cancer.一种用于预测卵巢癌预后的铁死亡相关基因的新型定义风险特征。
Front Mol Biosci. 2021 Apr 1;8:645845. doi: 10.3389/fmolb.2021.645845. eCollection 2021.
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Identification and Validation of a Novel Prognostic Signature Based on Ferroptosis-Related Genes in Ovarian Cancer.基于铁死亡相关基因的卵巢癌新型预后标志物的鉴定与验证
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TRIM46 contributes to high glucose-induced ferroptosis and cell growth inhibition in human retinal capillary endothelial cells by facilitating GPX4 ubiquitination.TRIM46 通过促进 GPX4 泛素化促进高糖诱导的人视网膜毛细血管内皮细胞铁死亡和细胞生长抑制。
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Ferroptosis-Related Long Noncoding RNAs as Prognostic Biomarkers for Ovarian Cancer.铁死亡相关长链非编码RNA作为卵巢癌的预后生物标志物
Front Oncol. 2022 Jun 9;12:888699. doi: 10.3389/fonc.2022.888699. eCollection 2022.

本文引用的文献

1
Trim46 knockout impaired neuronal architecture and caused hypoactive behavior in rats.Trim46基因敲除破坏了大鼠的神经元结构并导致其行为活动减退。
Dev Dyn. 2024 Jul;253(7):659-676. doi: 10.1002/dvdy.687. Epub 2024 Jan 9.
2
Review of the Role of Ferroptosis in Testicular Function.铁死亡在睾丸功能中的作用研究进展。
Nutrients. 2022 Dec 10;14(24):5268. doi: 10.3390/nu14245268.
3
When ferroptosis meets pathogenic infections.当铁死亡遇到致病感染时。
Trends Microbiol. 2023 May;31(5):468-479. doi: 10.1016/j.tim.2022.11.006. Epub 2022 Dec 7.
4
Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research.针对癌症治疗的细胞死亡途径:细胞坏死、细胞焦亡、铁死亡和铜死亡研究的新进展。
J Hematol Oncol. 2022 Dec 8;15(1):174. doi: 10.1186/s13045-022-01392-3.
5
TRIM46 aggravated high glucose-induced hyper permeability and inflammatory response in human retinal capillary endothelial cells by promoting IκBα ubiquitination.TRIM46通过促进IκBα泛素化加重高糖诱导的人视网膜毛细血管内皮细胞的高通透性和炎症反应。
Eye Vis (Lond). 2022 Sep 5;9(1):35. doi: 10.1186/s40662-022-00305-2.
6
Ferroptosis, necroptosis, and pyroptosis in the occurrence and development of ovarian cancer.铁死亡、坏死性凋亡和细胞焦亡在卵巢癌发生发展中的作用。
Front Immunol. 2022 Jul 25;13:920059. doi: 10.3389/fimmu.2022.920059. eCollection 2022.
7
SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells.SCD1/FADS2 脂肪酸去饱和酶平衡腹水来源卵巢癌细胞的脂代谢活性和氧化还原驱动的铁死亡。
Theranostics. 2022 Apr 24;12(7):3534-3552. doi: 10.7150/thno.70194. eCollection 2022.
8
Multi-omics approaches for biomarker discovery in early ovarian cancer diagnosis.多组学方法在早期卵巢癌诊断中的生物标志物发现。
EBioMedicine. 2022 May;79:104001. doi: 10.1016/j.ebiom.2022.104001. Epub 2022 Apr 16.
9
TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells.TRIM46 通过修饰 PHLPP2 的泛素化来激活 AKT/HK2 信号通路,从而促进肺癌细胞的糖酵解和化疗耐药性。
Cell Death Dis. 2022 Mar 30;13(3):285. doi: 10.1038/s41419-022-04727-7.
10
Targeting ferroptosis as a vulnerability in cancer.针对癌症中的铁死亡脆弱性。
Nat Rev Cancer. 2022 Jul;22(7):381-396. doi: 10.1038/s41568-022-00459-0. Epub 2022 Mar 25.

对铁死亡相关基因的综合分析表明,TRIM46是一种新型生物标志物,通过调节铁死亡和Wnt信号通路促进卵巢癌的进展。

Comprehensive analysis of ferroptosis-related genes indicates that TRIM46 is a novel biomarker and promotes the progression of ovarian cancer via modulating ferroptosis and Wnt signaling pathway.

作者信息

Liu Shuang, Xiao Chunmei, Rong Yue, Liu Mingbo, Yang Ke, Tang Jing, Wang Zhigang

机构信息

Department of Ultrasound, Women and Children's Hospital of Chongqing Medical University No. 120, Longshan Road, Yubei Distinct, Chongqing 401147, China.

Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University No. 120, Longshan Road, Yubei District, Chongqing 401147, China.

出版信息

Am J Cancer Res. 2024 Oct 15;14(10):4686-4707. doi: 10.62347/ONUY8904. eCollection 2024.

DOI:10.62347/ONUY8904
PMID:39553213
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11560837/
Abstract

Ovarian cancer (OC) is a common gynecological malignant tumor with poor prognosis. One form of controlled cell death that requires iron is ferroptosis. This study utilized TCGA data analysis to identify differentially expressed genes (DEGs) related to ferroptosis in OC, revealing 2,333 up-regulated and 4,073 down-regulated genes. Venn diagrams identified 64 up-regulated and 120 down-regulated ferroptosis-related DEGs (FR-DEGs), with 15 showing a significant correlation with overall patient survival. Further analyses explored the expression, mutations, and copy number variations of these 15 FR-DEGs across various cancer types, constructing interaction networks. Molecular subtypes in OC were classified using these 15 FR-DEGs, revealing two subtypes (C1 and C2). Survival analysis identified a risk model for the C1 group based on these genes. Experimental validation highlighted TRIM46 as a key gene, with knockdown inhibiting OC cell proliferation and migration. TRIM46 was also associated with changes in ferroptosis-related markers and demonstrated a close connection with the Wnt signaling pathway, validated through Western blot experiments. Overall, the study provided a comprehensive understanding of the role of DEGs related to ferroptosis in OC, offering valuable insights into disease mechanisms and potential therapeutic targets.

摘要

卵巢癌(OC)是一种常见的妇科恶性肿瘤,预后较差。一种需要铁的程序性细胞死亡形式是铁死亡。本研究利用TCGA数据分析来鉴定OC中与铁死亡相关的差异表达基因(DEGs),发现2333个上调基因和4073个下调基因。维恩图确定了64个上调和120个下调的铁死亡相关DEGs(FR-DEGs),其中15个与患者总生存期显著相关。进一步分析探讨了这15个FR-DEGs在各种癌症类型中的表达、突变和拷贝数变异,构建了相互作用网络。利用这15个FR-DEGs对OC中的分子亚型进行分类,发现了两个亚型(C1和C2)。生存分析基于这些基因确定了C1组的风险模型。实验验证突出了TRIM46作为关键基因,敲低该基因可抑制OC细胞增殖和迁移。TRIM46还与铁死亡相关标志物的变化有关,并通过蛋白质印迹实验证实与Wnt信号通路密切相关。总体而言,该研究全面了解了OC中与铁死亡相关的DEGs的作用,为疾病机制和潜在治疗靶点提供了有价值的见解。