FSP1: a key regulator of ferroptosis

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

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RNA modification: mechanisms and therapeutic targets

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Aug. 24, 2023

Abstract RNA modifications are dynamic and reversible chemical on substrate that regulated by specific modifying enzymes. They play important roles in the regulation of many biological processes various diseases, such as development cancer other diseases. With help advanced sequencing technologies, role has caught increasing attention human diseases scientific research. In this review, we briefly summarized basic mechanisms several common modifications, including m6A, m5C, m1A, m7G, Ψ, A-to-I editing ac4C. Importantly, discussed their potential functions cancer, neurological disorders, cardiovascular metabolic genetic developmental well immune disorders. Through “writing-erasing-reading” mechanisms, regulate stability, translation, localization pivotal disease-related mRNAs to manipulate disease development. Moreover, also highlighted review all currently available RNA-modifier-targeting small molecular inhibitors or activators, most which designed against m6A-related enzymes, METTL3, FTO ALKBH5. This provides clues for clinical therapy future study directions modification field. More in-depth studies further activators needed a thorough understanding epitranscriptomics diagnosis, treatment, prognosis

Language: Английский

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A bioinformatics analysis, pre-clinical and clinical conception of autophagy in pancreatic cancer: Complexity and simplicity in crosstalk

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106822 - 106822

Published: June 17, 2023

Pancreatic cancer (PC) is a serious gastrointestinal tract disease for which the 5-year survival rate less than 10%, even in developed countries such as USA. The genomic profile alterations and dysregulated biological mechanisms commonly occur PC. Macroautophagy/autophagy cell death process that maintained at basal level physiological conditions, whereas its often changes during tumorigenesis. function of autophagy human cancers dual can be oncogenic onco-suppressor. Autophagy potent controller tumorigenesis supportive PC escalates growth cells suppression mediate death. also determines metastasis cells, it control EMT affecting migration. Moreover, starvation hypoxia stimulate glycolysis, glycolysis induction mediated by enhancing Furthermore, protective stimulates drug resistance gemcitabine inhibition enhance radiosensitivity. degrade MHC-I to immune evasion regulates polarization macrophages tumor microenvironment. Modulation activity provided silibinin, ursolic acid, chrysin huaier treatment Non-coding RNAs are controllers improve therapy response patients. mitophagy shows dysregulation PC, proliferation cells. Therefore, bioinformatics analysis demonstrates autophagy-related proteins genes biomarkers.

Language: Английский

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Mechanisms of NAT10 as ac4C writer in diseases

Molecular Therapy — Nucleic Acids, Journal Year: 2023, Volume and Issue: 32, P. 359 - 368

Published: April 4, 2023

In the early stage, N4-acetylcytidine (ac4C) was regarded as a conservative nucleoside present on tRNA and rRNA. Recently, studies have shown that ac4C also exists in human yeast mRNA. N-Acetyltransferase-like protein 10 (NAT10) is first enzyme to be found catalyze production eukaryotic RNA has acetyltransferase activity RNA-binding activity. Here, we describe structure cellular localization of NAT10. Then, conclude active roles NAT10 "writer" mRNA stability translation efficiency, oocyte maturation, bone remodeling, fatty acid metabolism. With respect disease, focused promoting functions proliferation, metastasis, apoptosis multiple tumors. The immune regulatory role systemic lupus erythematosus maintenance virus replication influenza A are introduced. This review identifies potential target for diagnosis, therapy, prognosis clinical application.

Language: Английский

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N4‐Acetylcytidine Drives Glycolysis Addiction in Gastric Cancer via NAT10/SEPT9/HIF‐1α Positive Feedback Loop

Advanced Science, Journal Year: 2023, Volume and Issue: 10(23)

Published: June 16, 2023

Anti-angiogenic therapy has long been considered a promising strategy for solid cancers. Intrinsic resistance to hypoxia is major cause the failure of anti-angiogenic therapy, but underlying mechanism remains unclear. Here, it revealed that N4-acetylcytidine (ac4C), newly identified mRNA modification, enhances tolerance in gastric cancer (GC) cells by promoting glycolysis addiction. Specifically, acetyltransferase NAT10 transcription regulated HIF-1α, key factor cellular response hypoxia. Further, acRIP-sequencing, Ribosome profiling sequencing, RNA-sequencing, and functional studies confirm turn activates HIF-1 pathway subsequent glucose metabolism reprogramming mediating SEPT9 ac4C modification. The formation NAT10/SEPT9/HIF-1α positive feedback loop leads excessive activation induces Combined anti-angiogenesis inhibition attenuate inhibit tumor progression vivo. This study highlights critical roles regulation addiction proposes overcome combining apatinib with inhibition.

Language: Английский

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NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation

Circulation Research, Journal Year: 2023, Volume and Issue: 133(12), P. 989 - 1002

Published: Nov. 13, 2023

BACKGROUND: Heart failure, characterized by cardiac remodeling, is associated with abnormal epigenetic processes and aberrant gene expression. Here, we aimed to elucidate the effects mechanisms of NAT10 (N-acetyltransferase 10)-mediated N4-acetylcytidine (ac4C) acetylation during remodeling. METHODS: ac4C expression were detected in both human mouse subjects remodeling through multiple assays. Subsequently, acetylated RNA immunoprecipitation sequencing, thiol-linked alkylation for metabolic sequencing (SLAM-seq), ribosome (Ribo-seq) employed role ac4C-modified posttranscriptional regulation Additionally, functional experiments involving overexpression or knockdown conducted mice models challenged Ang II (angiotensin II) transverse aortic constriction. RESULTS: levels increased vitro vivo models, as well patients hypertrophy. Silencing inhibiting attenuated II-induced cardiomyocyte hypertrophy cardiofibroblast activation. Next-generation revealed changes humans global mRNA abundance, stability, translation efficiency. Mechanistically, could enhance stability efficiency CD47 ROCK2 transcripts upregulating their modification, thereby resulting an increase protein Furthermore, administration Remodelin, a inhibitor, has been shown prevent impairments subjected constriction suppressing fibrosis, hypertrophy, inflammatory responses, while also regulating (Rho coiled-coil containing kinase 2). CONCLUSIONS: Therefore, our data suggest that modulating epitranscriptomic processes, such NAT10, may be promising therapeutic target against

Language: Английский

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Emerging role of RNA acetylation modification ac4C in diseases: Current advances and future challenges

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 213, P. 115628 - 115628

Published: May 27, 2023

Language: Английский

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RNA modification in cardiovascular disease: implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 27, 2023

Abstract Cardiovascular disease (CVD) is the leading cause of death in world, with a high incidence and youth-oriented tendency. RNA modification ubiquitous indispensable cell, maintaining cell homeostasis function by dynamically regulating gene expression. Accumulating evidence has revealed role aberrant expression CVD caused dysregulated modification. In this review, we focus on nine common modifications: N 6 -methyladenosine (m A), 1 5-methylcytosine 5 C), 7 -methylguanosine G), 4 -acetylcytosine (ac pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, modifications U34 tRNA wobble. We summarize key regulators their effects expression, such as splicing, maturation, transport, stability, translation. Then, based classification CVD, mechanisms which occurs progresses through are discussed. Potential therapeutic strategies, therapy, reviewed these mechanisms. Herein, some (such stroke peripheral vascular disease) not included due to limited availability literature. Finally, prospective applications challenges discussed for purpose facilitating clinical Moreover, look forward more studies exploring roles future, there substantial uncultivated areas be explored.

Language: Английский

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NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression

Experimental Cell Research, Journal Year: 2023, Volume and Issue: 428(2), P. 113620 - 113620

Published: May 6, 2023

Language: Английский

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The role of organoids in cancer research

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Aug. 3, 2023

Organoids are established through in vitro 3D culture, and they can mimic the structure physiological functions of organs or tissues vivo. have attracted much attention recent years. They provide a reliable technology platform for cancer research treatment valuable preclinical model academic personalized medicine. A number studies confirmed that organoids great application prospects new drug development, screening, tumour mechanism research, precision In this review, we mainly focus on advances research. We also discussed opportunities challenges facing organoids, hoping to indicate directions development future.

Language: Английский

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