Emerging mechanisms and targeted therapy of ferroptosis in cancer

Wang, Haiyan; Cheng, Yan; Mao, Chao; Liu, Shuang; Xiao, Desheng; Huang, Jun; Tao, Yongguang

doi:10.1016/j.ymthe.2021.03.022

Cited by 160 publications

(119 citation statements)

References 291 publications

(345 reference statements)

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“…Existing evidence proves that ferroptosis plays an important role in the development of many diseases (7,8), such as cancer, neurodegenerative diseases, ischemia/reperfusion injury, acute kidney injury, atherosclerosis, chronic obstructive pulmonary disease, and immune system diseases. Therefore, as an evolutionary program offers various druggable nodes, ferroptosis is supposed to be an emerging way to cure many kinds of diseases (9)(10)(11)(12)(13)(14). Especially as a therapeutic model in cancer treatment and prevention of ischemic organ damage, ferroptosis has been convincingly established (15).…”

Section: Introductionmentioning

confidence: 99%

Knowledge Domain and Emerging Trends in Ferroptosis Research: A Bibliometric and Knowledge-Map Analysis

et al. 2021

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ObjectivesTo identify the cooperation and impact of authors, countries, institutions, and journals, evaluate the knowledge base, find the hotspot trends, and detect the emerging topics regarding ferroptosis research.MethodsThe articles and reviews related to ferroptosis were obtained from the Web of Science Core Collection on November 1, 2020. Two scientometric software (CiteSpace 5.7 and VOSviewer 1.6.15) were used to perform bibliometric and knowledge-map analysis.ResultsA total of 1,267 papers were included, in 466 academic journals by 6,867 authors in 438 institutions from 61 countries/regions. The ferroptosis-related publications were increasing rapidly. Cell Death & Disease published the most papers on ferroptosis, while Cell was the top co-cited journal, publication journals and co-cited journals were major in the molecular and biology fields. The United States and China were the most productive countries; meanwhile, the University of Pittsburgh, Columbia University and Guangzhou Medical University were the most active institutions. Brent R Stockwell published the most papers, while Scott J Dixon had the most co-citations; simultaneously, active cooperation existed in ferroptosis researchers. Ten references on reviews, mechanisms, and diseases were regarded as the knowledge base. Five main aspects of ferroptosis research included regulation mechanisms, nervous system injury, cancer, relationships with other types of cell death, and lipid peroxidation. The latest hotspots were nanoparticle, cancer therapy, iron metabolism, and in-depth mechanism. Notably Nrf2 might have turning significance. The emerging topics on ferroptosis research were the further molecular mechanism of ferroptosis and the wider application of ferroptosis-related disease with advanced technology.ConclusionThis study performed a full overview of the ferroptosis research using bibliometric and visual methods. The information would provide helpful references for scholars focusing on ferroptosis.

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Section: Introductionmentioning

confidence: 99%

Knowledge Domain and Emerging Trends in Ferroptosis Research: A Bibliometric and Knowledge-Map Analysis

et al. 2021

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“…The accumulation of iron, fatty acid supply, and lipid peroxidation induces cellular ferroptosis, resulting in iron-mediated oxidative damage of cell membranes such as the inner mitochondrial membrane with an increasing level of reactive oxygen species (ROS) [10][11][12]. This kind of ferroptotic injury plays an important role in the fate of tumor cells via damage-related molecular patterns and multiple cancer pathways [13,14]. For example, Zhang et al reported that ferroptosis regulates the tumor microenvironment by decreasing TAF activation and reducing TGF-β secretion in breast cancer [13].…”

Section: Introductionmentioning

confidence: 99%

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

Luo

Wang

et al. 2021

Cell Death Dis

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Long non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we further explored the function of RP11-89, a lncRNA discovered in the previous signature. Loss- and gain-of function experiments were performed using CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models. High-throughput RNA sequencing was conducted to identify dysregulated genes in bladder cancer cells with RP11-89 knockdown or overexpression. Regulation of RP11-89 on miR-129-5p and PROM2 was explored through luciferase reporter assay, RIP assay and RNA pull-down assay. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. We found that RP11-89 “sponges” miR-129-5p and upregulates PROM2. Elevated PROM2 in cells was associated with attenuated ferroptosis through iron export, formation of multivesicular bodies and less mitochondrial abnormalities. We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.

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“…Ferroptosis is a new form of regulated cell death induced by iron-dependent lipid peroxidation and with the characteristic of oxidative perturbations of the intracellular microenvironment ( Chen et al, 2021 ). A recent study suggested that ferroptosis might be developed as a natural and promising therapy against cancer ( Wang et al, 2021a ). However, up to now, the expression pattern and prognostic value of key regulators of ferroptosis especially the correlation between the expression levels of these genes and immune infiltration in pan-cancer are largely unclear.…”

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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Emerging mechanisms and targeted therapy of ferroptosis in cancer

Cited by 160 publications

References 291 publications

Knowledge Domain and Emerging Trends in Ferroptosis Research: A Bibliometric and Knowledge-Map Analysis

Knowledge Domain and Emerging Trends in Ferroptosis Research: A Bibliometric and Knowledge-Map Analysis

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

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

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