Ferroptosis contributes to the progression of female-specific neoplasms, from breast cancer to gynecological malignancies in a manner regulated by non-coding RNAs: Mechanistic implications DOI Creative Commons
Kiavash Hushmandi, Daniel J. Klionsky, Amir Reza Aref

et al.

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(4), P. 1159 - 1177

Published: May 20, 2024

Ferroptosis, a recently identified type of non-apoptotic cell death, triggers the elimination cells in presence lipid peroxidation and an iron-dependent manner. Indeed, ferroptosis-stimulating factors have ability suppressing antioxidant capacity, leading to accumulation reactive oxygen species (ROS) subsequent oxidative death cells. Ferroptosis is involved pathophysiological basis different maladies, such as multiple cancers, among which female-oriented malignancies attracted much attention recent years. In this context, it has also been unveiled that non-coding RNA transcripts, including microRNAs, long RNAs, circular RNAs regulatory interconnections with ferroptotic flux, controls pathogenic development diseases. Furthermore, potential employing these transcripts therapeutic targets during onset female-specific neoplasms modulate ferroptosis become research hotspot; however, molecular mechanisms functional alterations still require further investigation. The current review comprehensively highlights its association focus on how crosstalk affects pathogenesis malignancies, from breast cancer ovarian, cervical, endometrial neoplasms, suggesting novel decelerate even block expansion tumors.

Language: Английский

Ferroptosis as a potential target for cancer therapy DOI Creative Commons
Zhen Chen, Weilong Wang, Siti Razila Abdul Razak

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 24, 2023

Abstract Ferroptosis is a recently discovered essential type of cell death that mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests ferroptosis double-edged sword in human cancer. However, the precise underlying molecular mechanisms their differential roles tumorigenesis are unclear. Therefore, this review, we summarize briefly present key pathways ferroptosis, paying special attention to regulation as well its dual role an oncogenic tumor suppressor event various cancers. Moreover, multiple pharmacological activators summarized, prospect targeting cancer therapy further elucidated.

Language: Английский

Citations

105
CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis DOI Creative Commons
Yang Jiang, Junshuang Zhao, Rongqing Li

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Oct. 20, 2022

Ferroptosis is a novel form of iron-dependent cell death and participates in the malignant progression glioblastoma (GBM). Although circular RNAs (circRNAs) are found to play key roles ferroptosis via several mechanisms, including regulating iron metabolism, glutathione lipid peroxidation mitochondrial-related proteins, there many circRNAs need be found, they may become new molecular treatment target GBM.The expression levels circLRFN5, PRRX2 GCH1 were detected by qPCR, western blotting, immunohistochemistry. Lentiviral-based infections used overexpress or knockdown these molecules glioma stem cells (GSCs). The biological functions on GSCs MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium), 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, transwell, neurosphere formation assays, Extreme Limiting Dilution Analysis (ELDA) xenograft experiments. content was BODIPY 581/591 C11 (GSH) assay malondialdehyde (MDA) assay. mechanisms among studied RNA immunoprecipitation pull-down ubiquitination dual-luciferase reporter chromatin assay.We circRNA circLRFN5 downregulated GBM associated with patients' poor prognosis. CircLRFN5 overexpression inhibits viabilities, proliferation, neurospheres formation, stemness tumorigenesis inducing ferroptosis. Mechanistically, binds protein promotes its degradation ubiquitin-mediated proteasomal pathway. can transcriptionally upregulate GSCs, which suppressor generating antioxidant tetrahydrobiopterin (BH4).Our study as tumor-suppressive identified role GBM. potential biomarker for therapies ferroptosis-dependent therapy

Language: Английский

Citations

89
Ferroptosis in sepsis: The mechanism, the role and the therapeutic potential DOI Creative Commons

Lei XL,

Zhao GY,

Rongxian Guo

et al.

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

Published: Aug. 5, 2022

Sepsis is a common critical illness in the Intensive care unit(ICU) and its management treatment has always been major challenge medicine. The dysregulated host response to infection, causing systemic multi-organ multi-system damage main pathogenesis. Notably, intense stress during sepsis can lead metabolic disturbances of ions, lipids energy organism. Ferroptosis an iron-dependent, non-apoptotic cell death distinguished by disruption iron metabolism iron-dependent accumulation lipid peroxides. Mounting researches have established that ferroptosis essential part anti-inflammatory sepsis, drugs targeting ferroptosis-related molecules, such as inhibitors, are gradually proving their effectiveness sepsis. This paper summarizes reviews pathogenesis ferroptosis, regulatory network, vital involvement initiation related organ damage, finally discusses possible target provided above mechanisms, describes dilemmas well outlook, hope finding more links between providing new perspectives for future

Language: Английский

Citations

75
Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism DOI Creative Commons

Kaiyue Ding,

Chongbin Liu, Li Li

et al.

Chinese Medical Journal, Journal Year: 2023, Volume and Issue: unknown

Published: July 6, 2023

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to execution ferroptosis by triggering phospholipid peroxidation. Ferroptosis a type programmed cell death caused iron-dependent peroxidation lipids; ACSL4 glutathione peroxidase positively negatively regulate ferroptosis, respectively. In addition, essential regulator (FA) metabolism. remodels composition membranes, regulates steroidogenesis, balances eicosanoid biosynthesis. ACSL4-mediated metabolic reprogramming antitumor immunity have attracted much attention in cancer biology. Because it facilitates cross-talk between FA metabolism, also research hotspot diseases ischemia/reperfusion injuries. this review, we focus structure, biological function, unique role ASCL4 various human diseases. Finally, propose might be potential therapeutic target.

Language: Английский

Citations

74
Circular RNA FEACR inhibits ferroptosis and alleviates myocardial ischemia/reperfusion injury by interacting with NAMPT DOI Creative Commons
Jie Ju, Xinmin Li,

Xuemei Zhao

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: June 27, 2023

Abstract Background Emerging research has reported that circular RNAs (circRNAs) play important roles in cardiac cell death after myocardial ischemia and reperfusion (I/R). Ferroptosis, a new form of discovered recent years, been proven to participate the regulation I/R. This study used circRNA sequencing explore key ferroptosis I/R mechanisms potential function. Methods We performed circRNAs differentially expressed quantitative polymerase chain reactions determine expression different tissues detect subcellular localization cardiomyocyte. Gain- loss-of-function experiments were aimed examine function cardiomyocyte tissue damage RNA pull-down was applied proteins interacting with circRNA. Results Here, we identified ferroptosis-associated (FEACR) an underlying regulatory role ferroptosis. FEACR overexpression suppressed I/R-induced infarction ameliorated inhibition induces cardiomyocytes inhibits hypoxia reoxygenation-induced Mechanistically, directly bound nicotinamide phosphoribosyltransferase (NAMPT) enhanced protein stability NAMPT, which increased NAMPT-dependent Sirtuin1 (Sirt1) expression, promoted transcriptional activity forkhead box O1 (FOXO1) by reducing FOXO1 acetylation levels. further upregulated transcription ferritin heavy 1 ( Fth1 ), suppressor, resulted Conclusions Our finding reveals FEACR-mediated NAMPT-Sirt1-FOXO1-FTH1 signaling axis participates protects heart against injury. Thus, its downstream factors could be novel targets for alleviating ferroptosis-related injury ischemic diseases.

Language: Английский

Citations

57
ACSL4 as a Potential Target and Biomarker for Anticancer: From Molecular Mechanisms to Clinical Therapeutics DOI Creative Commons
Jun Hou, Changqing Jiang, Xudong Wen

et al.

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

Published: July 13, 2022

Cancer is a major public health problem around the world and key leading cause of death in world. It well-known that glucolipid metabolism, immunoreaction, growth/death pattern cancer cells are markedly different from normal cells. Recently, acyl-CoA synthetase long-chain family 4 (ACSL4) found be participated activation long chain fatty acids immune signaling transduction, ferroptosis, which can promising potential target biomarker for anticancer. Specifically, ACSL4 inhibits progress lung cancer, estrogen receptor (ER) positive breast cervical up-regulation improve sensitivity to ferroptosis by enhancing accumulation lipid peroxidation products lethal reactive oxygen species (ROS). However, it undeniable high expression ER negative hepatocellular carcinoma, colorectal prostate also related with tumor cell proliferation, migration, invasion. In present review, we provide an update on understanding controversial roles

Language: Английский

Citations

50
Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms DOI Creative Commons

Emad Heydarnia,

Zahra Dorostgou,

Neda Hedayati

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 10, 2024

Abstract Cervical cancer (CC) is a common gynecologic malignancy, accounting for significant proportion of women death worldwide. Human papillomavirus (HPV) infection one the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible disease expansion. Circular RNAs (circRNAs), which known as particular subset non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported be involved in progression diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs strong correlation pathogenesis through regulating substantial signaling pathways. Also, these molecules can considered promising biomarkers therapeutic targets diagnosis/prognosis treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/β-catenin, MAPK, PI3K/Akt/mTOR pathways, well angiogenesis metastasis, by interfere development. Then, diagnostic, prognostic, potentials ncRNA will highlighted depth.

Language: Английский

Citations

13
Targeting ferroptosis using Chinese herbal compounds to treat respiratory diseases DOI Creative Commons

Mengjiao Xu,

Di Zhang, Jun Yan

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155738 - 155738

Published: June 1, 2024

Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, autophagy, characterised by iron, reactive oxygen species, lipid peroxide accumulation, as well glutathione (GSH) depletion GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis the onset progression respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, fibrosis, cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in treatment owing natural properties potential efficacy. These can effectively regulate modulating several key signalling pathways such system Xc

Language: Английский

Citations

11
Competing endogenous RNA networks and ferroptosis in cancer: novel therapeutic targets DOI Creative Commons

Fatemeh Nejadi Orang,

Mahdi Abdoli Shadbad

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 22, 2024

Abstract As a newly identified regulated cell death, ferroptosis is metabolically driven process that relies on iron and associated with polyunsaturated fatty acyl peroxidation, elevated levels of reactive oxygen species (ROS), mitochondrial damage. This distinct death dysregulated in various cancers; activating malignant cells increases cancer immunotherapy chemoradiotherapy responses across different malignancies. Over the last decade, accumulating research has provided evidence cross-talk between non-coding RNAs (ncRNAs) competing endogenous RNA (ceRNA) networks highlighted their significance developing progressing Aside from pharmaceutical agents to regulate ferroptosis, recent studies have shed light potential restoring ferroptosis-related ceRNA treatment. The present study provides comprehensive up-to-date review significance, pathways, role chemoradiotherapy, biogenesis, ferroptosis-regulating cancers. insights can offer authorship state-of-the-art findings future perspectives regarding implication treatment determining prognosis affected patients.

Language: Английский

Citations

10
Relationship between miRNA and ferroptosis in tumors DOI Creative Commons

Shang‐Ming Dai,

Feng‐Jiao Li,

Hui‐Zhi Long

et al.

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

Published: Nov. 4, 2022

Malignant tumor is a major killer that seriously endangers human health. At present, the methods of treating tumors include surgical resection, chemotherapy, radiotherapy and immunotherapy. However, survival rate patients still very low due to complicated mechanism occurrence development high recurrence rate. Individualized treatment will be main direction in future. Because only by understanding molecular differentially expressed genes can we carry out accurate improve therapeutic effect. MicroRNA (miRNA) kind small non coding RNA, which regulates gene expression at mRNA level plays key role regulation. Ferroptosis programmed death caused iron dependent lipid peroxidation, different from apoptosis, necrosis other cell modes. Now it has been found ferroptosis an important drug resistance. More more studies have miRNAs regulate resistance through ferroptosis. Therefore, this review, briefly outlined, relationship between reviewed.

Language: Английский

Citations

34