Ferroptosis in tumors and its relationship to other programmed cell death: role of non-coding RNAs

Zhang, Qi; Fan, Xiaolan; Zhang, Xinyu; Ju, Shaoqing

doi:10.1186/s12967-023-04370-6

Cited by 17 publications

(4 citation statements)

References 176 publications

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“…Our previous study demonstrated a critical role of CD71, becoming part of an aberrant gene/protein expression pattern upon neoplastic transformation and malignant progression of ATC, which strongly candidate it as potential direct or indirect therapeutic target [ 40 ]. In particular, the core of its therapeutic potential could be also the close relationship with iron-depending cell death [ 56 ]. For instance, CD71 is mainly involved in iron homeostasis, binding serum transferrin and thus contributing to the increase of the small pool of Fe 2+ (referred to as the labile iron pool), able to generate ROS, which in turn initiate lipid peroxidation and eventually lead to ferroptosis [ 15 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance

D’Aprile,

Denaro,

Pavone

et al. 2023

J Transl Med

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Background Follicular thyroid cancer (FTC) is a prevalent form of differentiated thyroid cancer, whereas anaplastic thyroid cancer (ATC) represents a rare, fast-growing, undifferentiated, and highly aggressive tumor, posing significant challenges for eradication. Ferroptosis, an iron-dependent cell death mechanism driven by the excessive production of reactive oxygen species and subsequent lipid peroxidation, emerges as a promising therapeutic strategy for cancer. It has been observed that many cancer cells exhibit sensitivity to ferroptosis, while some other histotypes appear to be resistant, by counteracting the metabolic changes and oxidative stress induced by iron overload. Methods Here we used human biopsies and in vitro approaches to analyse the effects of iron-dependent cell death. We assessed cell proliferation and viability through MTT turnover, clonogenic assays, and cytofluorimetric-assisted analysis. Lipid peroxidation assay and western blot were used to analyse molecular mechanisms underlying ferroptosis modulation. Two distinct thyroid cancer cell lines, FTC-133 (follicular) and 8505C (anaplastic), were utilized. These cell lines were exposed to ferroptosis inducers, Erastin and RSL3, while simulating an iron overload condition using ferric ammonium citrate. Results Our evidence suggests that FTC-133 cell line, exposed to iron overload, reduced their viability and showed increased ferroptosis. In contrast, the 8505C cell line seems to better tolerate ferroptosis, responding by modulating CD71, which is involved in iron internalization and seems to have a role in resistance to iron overload and consequently in maintaining cell viability. Conclusions The differential tolerance to ferroptosis observed in our study may hold clinical implications, particularly in addressing the unmet therapeutic needs associated with ATC treatment, where resistance to ferroptosis appears more pronounced compared to FTC.

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Section: Discussionmentioning

confidence: 99%

Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance

D’Aprile,

Denaro,

Pavone

et al. 2023

J Transl Med

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“…However, given the extraordinary complexity and heterogeneity of this group of disorders, sensitivity to ferroptosis may vary greatly among different types of cancer cells. For example, p53, which exerts a critical role in inhibiting tumorigenesis and other cancer processes such as invasion, metastasis, and metabolism, has been reported to control ferroptosis-related genes to prevent tumor growth [ 63 , 64 ]. However, as discussed in detail in Section 4.6 it recently emerged that p53 has opposing effects on ferroptosis regulation in different tumor cells.…”

Section: Ferroptosis As a Biological Program: Features And General Me...mentioning

confidence: 99%

Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors

Punziano,

Trombetti,

Cesaro

et al. 2024

Antioxidants

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Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis and is related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, and ischemia–reperfusion injuries. Ferroptosis is linked to iron accumulation, eliciting dysfunction of antioxidant systems, which favor the production of lipid peroxides, cell membrane damage, and ultimately, cell death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against iron excess and/or lipid-derived ROS. Here, we discuss the interaction between the metabolic pathways of ferroptosis and antioxidant systems, with a particular focus on transcription factors implicated in the regulation of ferroptosis, either as triggers of lipid peroxidation or as ferroptosis antioxidant defense pathways.

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“…With the advancement of cancer biology research, the interaction between programmed cell death (PCD) and malignant tumors has received widespread attention, being considered a crucial component in the occurrence of malignant tumors ( 9 , 10 ). As research progresses, an increasing number of researchers are focusing on the correlation between PCD and osteosarcoma occurrence ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

A novel prognostic signature related to programmed cell death in osteosarcoma

Jiang,

Xu,

Wang

et al. 2024

Front. Immunol.

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BackgroundOsteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death (PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model.MethodWe retrieved osteosarcoma patient samples from TARGET and GEO databases, and manually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessed mRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments.ResultIn our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes—CLTCL1, EDIL3, and SQLE—resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets.ConclusionThe five genes constituting the OS-PCDS model—CLTCL1, MTM1, MLH1, EDIL3, and SQLE—were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma.

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Ferroptosis in tumors and its relationship to other programmed cell death: role of non-coding RNAs

Cited by 17 publications

References 176 publications

Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance

Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance

Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors

A novel prognostic signature related to programmed cell death in osteosarcoma

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