Biochimica et Biophysica Acta (BBA) - General Subjects, Journal Year: 2024, Volume and Issue: unknown, P. 130714 - 130714
Published: Sept. 1, 2024
Language: Английский
Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)
Published: Oct. 16, 2023
Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.
Language: Английский
Citations
62
Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)
Published: Sept. 19, 2023
Glioma exhibit heterogeneous susceptibility for targeted ferroptosis. How circRNAs alterations in glioma promote iron metabolism and ferroptosis defense remains unclarified.The highly enriched glioblastoma (GBM) were obtained through analysis of sequencing datasets. Quantitative real-time PCR (qRT-PCR) was used to determine the expression circRNF10 normal brain tissue. Both gain-of-function loss-of-function studies assess effects on using vitro vivo assays. The hypothesis that ZBTB48 promotes established bioinformatics functional RNA pull-down immunoprecipitation (RIP) assays performed examine interaction between target proteins including ZBTB48, MKRN3 IGF2BP3. posttranslational modification mechanism verified coimmunoprecipitation (co-IP) ubiquitination transcription activation HSPB1 IGF2BP3 by confirmed luciferase reporter gene chromatin (ChIP) stabilizing effect explored actinomycin D assay. Finally, a series experiments explore influences progression.A novel circular RNA, hsa_circ_0028912 (named circRNF10), which is significantly upregulated tissues correlated with patients' poor prognosis. Through integrated circRNA-proteins datasets results, we reveal as transcriptional factor binding circRNF10, notably promoting upregulation remodel facilitates launch circRNF10/ZBTB48/IGF2BP3 positive feedback loop GSCs. Additionally, can competitively bind block E3 ubiquitin ligase activity enhance expression. Consequently, circRNF10-overexpressed stem cells (GSCs) display lower Fe2+ accumulation, selectively priming tumors evading.Our research presents abnormal causing molecular metabolic change glioma, leverage discover therapeutically exploitable vulnerability
Language: Английский
Citations
23
Cancer Letters, Journal Year: 2024, Volume and Issue: 597, P. 217059 - 217059
Published: June 13, 2024
5-Methylcytosine (m5C) methylation is a significant post-transcriptional modification that play crucial role in the development and progression of numerous cancers. Whereas functions molecular mechanisms underlying m5C gliomas remain unclear. This study dedicated to explore changes levels clinical significance writer NSUN4 gliomas. We found high were negatively related prognosis patients with glioma. Moreover, gain- loss-of-function experiments revealed enhancing mRNA promote malignant Mechanistically speaking, NSUN4-mediated alterations regulated ALYREF binding CDC42 mRNA, thereby impacting stability CDC42. also demonstrated promoted glioma proliferation, migration, invasion by activating PI3K-AKT pathway. Additionally, rescue proved overexpression weaken inhibitory effect knockdown on vitro vivo. Our findings elucidated regulate its stability, driving provides theoretical support for targeted treatment
Language: Английский
Citations
9
Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
The invasion and metastasis of pancreatic cancer (PC) are key factors contributing to disease progression poor prognosis. This process is primarily driven by EMT, which has been the focus recent studies highlighting role long non-coding RNAs (lncRNAs) as crucial regulators EMT. However, mechanisms lncRNAs influence invasive multifaceted, extending beyond EMT regulation alone. review aims characterize affecting in cancer. We summarize regulatory roles across multiple molecular pathways highlight their translational potential, considering implications for clinical applications diagnostics therapeutics. focuses on three principal scientific themes. First, we orchestrate various signaling pathways, such TGF-β/Smad, Wnt/β-catenin, Notch, regulate changes associated with thereby enhancing cellular motility invasivenes. Second, effects autophagy ferroptosis discuss exosomal tumor microenvironment behavior neighboring cells promote cell invasion. Third, emphasize RNA modifications (such m6A m5C methylation) stabilizing capacity mediate PC. Lastly, potential these findings, emphasizing inherent challenges using biomarkers therapeutic targets, while proposing prospective research strategies.
Language: Английский
Citations
1
International Immunopharmacology, Journal Year: 2024, Volume and Issue: 128, P. 111495 - 111495
Published: Jan. 21, 2024
Language: Английский
Citations
5
Carcinogenesis, Journal Year: 2024, Volume and Issue: 45(7), P. 487 - 499
Published: Feb. 23, 2024
Abstract Ferroptosis is a new form of regulated cell death caused by the iron-dependent peroxidation phospholipids and related to metabolism, redox homeostasis various signalling pathways cancer. The long non-coding RNA (lncRNA) KB-1460A1.5 acts as tumour suppressor gene regulate growth in gliomas, but its molecular network regulatory mechanism still unclear. In this study, we found that can induce ferroptosis glioma enhance sensitivity RSL3, inducer. Tandem mass tag proteomics nontargeted metabolomics suggest affects polyunsaturated fatty acid metabolic processes. Gas chromatography–mass spectrometry-based medium- long-chain acid-targeted confirmed upregulation decreased levels monounsaturated acids, oleic (OA) palmitoleic (PO) cells. addition OA PO restored KB-1460A1.5-induced cellular ferroptosis. Molecularly, inhibited mammalian target rapamycin pathway suppress expression downstream sterol element-binding protein 1 (SREBP-1), thereby attenuating stearoyl-CoA desaturase-1 (SCD1)-mediated desaturation acids. Finally, an animal model subcutaneous could inhibit progression, SREBP-1/SCD1 conclusion, increasing level promote induction oxidative stress cancer cells through SREBP-1/SCD1-mediated adipogenesis, demonstrating therapeutic potential preclinical models.
Language: Английский
Citations
4
Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(13)
Published: July 1, 2024
Hepatocellular carcinoma (HCC), a prevalent malignancy worldwide, poses significant challenges in terms of prognosis, necessitating innovative therapeutic approaches. Ferroptosis offers notable advantages over apoptosis, holding promise as novel approach for HCC complexities. Moreover, while the interaction between long non-coding RNAs (lncRNAs) and mRNAs is pivotal various physiological pathological processes, their involvement ferroptosis remains relatively unexplored. In this study, we constructed ferroptosis-related lncRNA-mRNA correlation network using Pearson analysis. Notably, SLC7A11-AS1/SLC7A11 pair, exhibiting high correlation, was identified. Bioinformatics analysis revealed expression levels pair key clinical characteristics patients, including gender, pathology, Ishak scores tumour size. And poor prognosis associated with pair. Functional experiments demonstrated that SLC7A11-AS1, by binding to 3'UTR region SLC7A11 mRNA, enhanced its stability, thereby promoting cell growth resistance erastin- induced ferroptosis. Additionally, vivo studies confirmed SLC7A11-AS1 knockdown potentiated inhibitory effects erastin on growth. Overall, our findings suggest targeting holds potential strategy patients.
Language: Английский
Citations
4
Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)
Published: Jan. 13, 2025
Recent studies indicate that N6-methyladenosine (m6A) RNA modification may regulate ferroptosis in cancer cells, while its molecular mechanisms require further investigation. Liquid Chromatography-Tandem Mass Spectrometry (HPLC/MS/MS) was used to detect changes m6A levels cells. Transmission electron microscopy and flow cytometry were mitochondrial reactive oxygen species (ROS). sequencing (RNA-seq) employed analyze the factors regulating ferroptosis. Chromatin immunoprecipitation (ChIP) assess binding of regulatory SLC7A11 promoter, a Dual-Luciferase reporter assay measured promoter activity SLC7A11. The dm6ACRISPR system utilized for demethylation specific transcripts. Cancer Genome Atlas Program (TCGA) database immunohistochemistry validated role METTL3/SLC7A11 axis progression. methyltransferase METTL3 upregulated during cell facilitated erastin-induced by enhancing ROS. Mechanistic showed negatively regulated transcription Specifically, induced H3K27 trimethylation suppressing mRNA stability demethylases KDM6B. Furthermore, suppressed expression GATA3, which putative site at - 597 590 promoter. decreased precursor GATA3 through m6A/YTHDF2-dependent recruitment 3'-5' exoribonuclease Dis3L2. Targeted KDM6B using significantly increased Moreover, factor YY1 responsible upregulation promoter-proximal site. In vivo clinical data supported positive roles tumor growth modulate an m6A-dependent manner. This study provides novel potential strategy experimental support future treatment cancer.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: March 21, 2025
Normal cells begin to grow indefinitely and immortalize form tumor after an external stimulus resulting in a genetic mutation. Effective killing of is the basis various cancer therapies. Ferroptosis class cell death types dependent on iron cellular lipid peroxidation. Tumors themselves are iron-dependent, conventional radiotherapy also sensitizes ferroptosis. Increasing sensitivity ferroptosis may be potential therapeutic strategy overcome resistance mechanisms therapy. Long noncoding RNAs (LncRNAs) transcripts more than 200 nucleotides length that regulate gene expression at multiple levels involved biological processes such as differentiation, cycle arrest, maintenance stemness. Recent studies have found lncRNAs through influence or ameliorate chemotherapeutic agents. With continuous maturation nanomaterials technology, it provide new means for treatment by regulating ferroptosis-related inside tumors well increasing Fe 2+ ROS tumors. In this paper, we systematically introduce regulatory mechanism ferroptosis, role immunotherapy application combined with nanomaterials, which provides perspectives
Language: Английский
Citations
0
Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103628 - 103628
Published: April 1, 2025
Nitrogen mustard (NM) causes severe skin injury that is lack of effective and targeted therapies. Vitamin D3 (VD3) emerges as a promising treatment option for NM-caused dermal toxicity; however, the underlying mechanisms are currently unclear. Herein, we identified NM markedly promoted ferroptosis by measurement decreased cell viability, glutathione, glutathione peroxidase 4 solute carrier family 7 member 11 levels, increased ROS, lipid iron/Fe2+ malondialdehyde contents in vitro vivo. Ferrostin-1 (Fer-1, inhibitor) attenuated death keratinocytes. Meanwhile, significantly inhibited phosphorylation AKT1 glycogen synthase kinase 3β (GSK3β) nuclear factor erythroid 2-related 2 (Nrf2) translocation, LINC00707 expression. Furthermore, NM-induced keratinocytes was abolished with agonists Nrf2 (tBHQ) (SC79), inhibitor GSK3β (AR-A014418), overexpression or knockdown. Mechanistically, directly bound protein domain suppressed its activated thereby inactivating Nrf2, subsequently inducing NM-treated Moreover, VD3 notably expression, inactivated GSK3β, translocation cytotoxicity induced The protective effects against toxicity were blocked erastin (a inducer), siRNA, enhanced knockdown Fer-1 In conclusion, ameliorated inhibiting ferroptosis, which partially mediated through LINC00707-AKT1-GSK3β-Nrf2 signaling pathway.
Language: Английский
Citations
0