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Novel insights into ferroptosis: Implications for age-related diseases.

ABSTRACT: Rapid increase in aging populations is an urgent problem because older adults are more likely to suffer from disabilities and age-related diseases (ARDs), burdening healthcare systems and society in general. ARDs are characterized by the progressive deterioration of tissues and organs over time, eventually leading to tissue and organ failure. To date, there are no effective interventions to prevent the progression of ARDs. Hence, there is an urgent need for new treatment strategies. Ferroptosis, an iron-dependent cell death, is linked to normal development and homeostasis. Accumulating evidence, however, has highlighted crucial roles for ferroptosis in ARDs, including neurodegenerative and cardiovascular diseases. In this review, we a) summarize initiation, regulatory mechanisms, and molecular signaling pathways involved in ferroptosis, b) discuss the direct and indirect involvement of the activation and/or inhibition of ferroptosis in the pathogenesis of some important diseases, and c) highlight therapeutic targets relevant for ARDs.

SUBMITTER: Zhou RP

PROVIDER: S-EPMC7667696 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Novel insights into ferroptosis: Implications for age-related diseases.

Zhou Ren-Peng RP Chen Yong Y Wei Xin X Yu Bin B Xiong Zhi-Gang ZG Lu Chao C Hu Wei W

Theranostics 20201026 26

Rapid increase in aging populations is an urgent problem because older adults are more likely to suffer from disabilities and age-related diseases (ARDs), burdening healthcare systems and society in general. ARDs are characterized by the progressive deterioration of tissues and organs over time, eventually leading to tissue and organ failure. To date, there are no effective interventions to prevent the progression of ARDs. Hence, there is an urgent need for new treatment strategies. Ferroptosis, ...[more]

PMID: 33204324

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Project description:BackgroundLung cancer has been the focus of attention for many researchers in recent years due to its leading contribution to cancer-related death worldwide, with lung adenocarcinoma (LUAD) being the most common histological type. Ferroptosis, a novel iron-dependent form of regulated cell death, can be induced by sorafenib. Emerging evidence shows that triggering ferroptosis has potential as a cancer therapy. This work aimed to build a ferroptosis-related gene signature for predicting the outcome of LUAD.MethodsThe TCGA-LUAD dataset was set as the training cohort, and the GSE72094 and GSE68465 datasets were set as the validation cohorts. Sixty-two ferroptosis-related genes were retrieved from the literature. A univariate Cox regression model was constructed for the training cohort to preliminarily screen for potential prognostic ferroptosis-related genes. A gene signature was generated from a LASSO Cox regression model and assessed with the training and validation cohorts through Kaplan-Meier, Cox, and ROC analyses. In addition, the correlation between the risk score and autophagy-related genes was determined by the Pearson test. Finally, GSEA and immune infiltrating analyses were performed to better study the functional annotation of the signature and the role of each kind of immune cell.ResultsA ten-gene signature was constructed from the training cohort and validated in three cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognostic value in LUAD. Moreover, a ROC analysis conducted with all cohort data confirmed the predictive ability of the ten-gene signature for LUAD prognosis. A total of 62.85% (308/490) of autophagy-related genes were found to be significantly correlated with risk scores. GSEA detailed the exact pathways related to the gene signature, and immune-infiltrating analyses identified crucial roles for resting mast cells and resting dendritic cells in the prognosis of LUAD.ConclusionsWe identified a novel ferroptosis-related ten-gene signature (PHKG2, PGD, PEBP1, NCOA4, GLS2, CISD1, ATP5G3, ALOX15, ALOX12B, and ACSL3) that can accurately predict LUAD prognosis and is closely linked to resting mast cells and resting dendritic cells.

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Novel insights into ferroptosis: Implications for age-related diseases.

Publications

Novel insights into ferroptosis: Implications for age-related diseases.

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