Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(6)
Published: June 1, 2022
Language: Английский
Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)
Published: July 27, 2021
Abstract N6-methyladenosine (m6A) has emerged as an abundant modification throughout the transcriptome with widespread functions in protein-coding and noncoding RNAs. It affects fates of modified RNAs, including their stability, splicing, and/or translation, thus plays important roles posttranscriptional regulation. To date, m6A methyltransferases have been reported to execute deposition on distinct RNAs by own or forming different complexes additional partner proteins. In this review, we summarize function these regulating key genes pathways cancer biology. We also highlight progress use mediating therapy resistance, chemotherapy, targeted therapy, immunotherapy radiotherapy. Finally, discuss current approaches clinical potential methyltransferase-targeting strategies.
Language: Английский
Citations
187
Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)
Published: Jan. 28, 2022
Abstract N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic recent years. M6A plays multifunctional roles normal abnormal biological processes, its role may vary greatly depending on position m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis ferroptosis, which involve breakdown plasma membrane. Based implications methylation PCD, regulators functional were comprehensively studied reported. In this review, we focus high-complexity links between different types PCD pathways, are then closely associated with initiation, progression resistance cancer. Herein, clarifying relationship is great significance to provide novel strategies for cancer treatment, potential prospect clinical application.
Language: Английский
Citations
176
Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 66, P. 100916 - 100916
Published: Dec. 29, 2022
Language: Английский
Citations
165
Cancer Communications, Journal Year: 2022, Volume and Issue: 42(4), P. 287 - 313
Published: Feb. 20, 2022
Resistance to ferroptosis, a regulated cell death caused by iron-dependent excessive accumulation of lipid peroxides, has recently been linked lung adenocarcinoma (LUAD). Intracellular antioxidant systems are required for protection against ferroptosis. The purpose the present study was investigate whether and how extracellular system desensitizes LUAD cells ferroptosis.Established human fibroblasts MRC-5, WI38, H1650, PC9, H1975, H358, A549, H1299 lines, tumor matched normal adjacent tissues LUAD, plasma from healthy individuals patients were used in this study. Immunohistochemistry immunoblotting analyze protein expression, quantitative reverse transcription-PCR mRNA expression. Cell viability, death, reactive oxygen species generation measured evaluate responses Exosomes observed using transmission electron microscope. localization arachidonic acid (AA) detected click chemistry labeling followed confocal microscopy. Interactions between RNAs proteins RNA pull-down, immunoprecipitation photoactivatable ribonucleoside-enhanced crosslinking methods. Proteomic analysis RNA-regulated proteins, metabolomic performed metabolites. Cell-derived xenograft, patient-derived cell-implanted intrapulmonary mouse models plasma/tissue specimens validate molecular mechanism.Plasma exosome specifically reduced peroxidation desensitized A potential explanation is that exosomal circRNA_101093 (cir93) maintained an elevation intracellular cir93 modulate AA, poly-unsaturated fatty critical ferroptosis-associated increased membrane. Mechanistically, interacted with acid-binding 3 (FABP3), which transported AA facilitated its reaction taurine. Thus, global reduced, whereas N-arachidonoyl taurine (NAT, product taurine) induced. Notably, role NAT suppressing incorporation into membrane also revealed. In pre-clinical vivo models, reducing improved ferroptosis-based treatment.Exosome essential desensitizing blocking may be helpful future treatment.
Language: Английский
Citations
128
Cancer Cell International, Journal Year: 2022, Volume and Issue: 22(1)
Published: Jan. 7, 2022
Abstract Background N6-methyladenosine (m 6 A) has emerged as a significant regulator of the progress various cancers. However, its role in lung adenocarcinoma (LUAD) remains unclear. Here, we explored biological function and underlying mechanism methyltransferase-like 3 (METTL3), main catalyst m A, LUAD progression. Methods The expression METTL3, YTHDF1 SLC7A11 were detected by immunochemistry or/and online datasets patients. effects METTL3 on cell proliferation, apoptosis ferroptosis assessed through vitro loss-and gain-of-function experiments. vivo effect tumorigenesis was evaluated using xenograft mouse model. MeRIP-seq, RNA immunoprecipitation stability assay conducted to explore molecular LUAD. Results results showed that A level, well methylase both significantly elevated patients cancer cells. Functionally, found could promote proliferation inhibit different models, while knockdown suppressed growth cell-derived xenografts. Mechanistically, solute carrier 7A11 (SLC7A11), subunit system Xc − , identified direct target mRNA-seq MeRIP-seq. METTL3-mediated modification stabilize mRNA translation, thus promoting inhibiting ferroptosis, novel form programmed death. Additionally, demonstrated YTHDF1, reader, recruited enhance modification. Moreover, positively correlated with tissues. Conclusions These findings reinforced oncogenic progression revealed correlation ferroptosis; these also indicate is promising diagnosis therapy.
Language: Английский
Citations
120
Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)
Published: Oct. 30, 2022
Abstract Ferroptosis is a form of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation, earlier studies identified glutathione peroxidase 4 (GPX4) as an essential regulator this process. plays role in tumors, degenerative diseases, ischemia-reperfusion injury. However, researchers have found that inhibition GPX4 does not entirely suppress ferroptosis certain or cells express resistance to agonists inhibit GPX4. As research progresses, it has been discovered there are multiple regulatory pathways for independent The study GPX4-independent can better target prevent treat various diseases. Here, the currently inhibited pulmonary GPX4-dependent will be reviewed.
Language: Английский
Citations
109
Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 753 - 764
Published: June 24, 2023
Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules ferroptosis. FSP1 functions through FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and vitamin K redox cycle. regulated by upstream factors, including transcription factors noncoding RNA (ncRNA), subject to epigenetic modifications, which affect progress FSP1-related diseases. closely associated with poor prognosis malignant tumors plays an important role in disease treatment. This review aims provide a comprehensive understanding ferroptosis regulation summarizing pathways, possible mechanisms involving FSP1, relationship between
Language: Английский
Citations
106
International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(5), P. 1829 - 1843
Published: Jan. 1, 2022
Ferroptosis is a novel form of programmed cell death, and it characterized by iron-dependent oxidative damage, lipid peroxidation reactive oxygen species accumulation. Notable studies have revealed that ferroptosis plays vital roles in tumor occurrence abundant cells can inhibit progression. Recently, some noncoding RNAs (ncRNAs), particularly microRNAs, long RNAs, circular been shown to be involved biological processes ferroptosis, thus affecting cancer growth. However, the definite regulatory mechanism this phenomenon still unclear. To clarify issue, increasing focused on ncRNAs initiation development role progression various cancers, such as lung, liver, breast cancers. In review, we systematically summarized relationship between ferroptosis-associated Moreover, additional evidence needed identify ferroptosis-related This review will help us understand may provide new ideas for exploring diagnostic therapeutic biomarkers future.
Language: Английский
Citations
103
Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(6), P. 1094 - 1106
Published: April 14, 2022
Abstract Ferroptosis is a recently defined form of regulated cell death, which biochemically and morphologically distinct from traditional forms programmed death such as apoptosis or necrosis. It driven by iron, reactive oxygen species, phospholipids that are oxidatively damaged, ultimately resulting in mitochondrial damage breakdown membrane integrity. Numerous cellular signaling pathways molecules involved the regulation ferroptosis, including enzymes control redox status. Alterations ferroptosis-regulating network can contribute to development various diseases, cancer. Evidence suggests ferroptosis commonly suppressed cancer cells, allowing them survive progress. However, cells resistant common chemotherapeutic drugs seem be highly susceptible inducers, highlighting great potential pharmacologic modulation for treatment. Non-coding RNAs (ncRNAs) considered master regulators processes, particularly where they have been implicated all hallmarks Recent work also demonstrated their involvement molecular ferroptosis. Hence, ncRNA-based therapeutics represent an exciting alternative modulate therapy. This review summarizes ncRNAs highlights underlying mechanisms light therapeutic applications.
Language: Английский
Citations
98
Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)
Published: Dec. 10, 2023
Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt
Language: Английский
Citations
77