Amino acid metabolism in health and disease

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

Published: Sept. 13, 2023

Abstract Amino acids are the building blocks of protein synthesis. They structural elements and energy sources cells necessary for normal cell growth, differentiation function. acid metabolism disorders have been linked with a number pathological conditions, including metabolic diseases, cardiovascular immune cancer. In case tumors, alterations in amino can be used not only as clinical indicators cancer progression but also therapeutic strategies. Since growth development tumors depend on intake foreign acids, more studies targeted tumor-related to selectively kill tumor cells. Furthermore, immune-related confirmed that regulates function effector T regulatory cells, affecting Therefore, studying associated disease identifying targets pathways may helpful treatment. This article mainly focuses research tumor-oriented reviews progress diseases related metabolism, order provide theoretical basis therapy metabolism.

Language: Английский

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N6-methyladenosine methyltransferases: functions, regulation, and clinical potential

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

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Inhibition of METTL3 attenuates renal injury and inflammation by alleviating TAB3 m6A modifications via IGF2BP2-dependent mechanisms

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(640)

Published: April 13, 2022

The role of N6-methyladenosine (m6A) modifications in renal diseases is largely unknown. Here, we characterized the N6-adenosine-methyltransferase-like 3 (METTL3), whose expression elevated tubules different acute kidney injury (AKI) models as well human biopsies and cultured tubular epithelial cells (TECs). METTL3 silencing alleviated inflammation programmed cell death TECs response to stimulation by tumor necrosis factor-α (TNF-α), cisplatin, lipopolysaccharide (LPS), whereas overexpression had opposite effects. Conditional knockout from mouse kidneys attenuated cisplatin- ischemic/reperfusion (I/R)-induced dysfunction, injury, inflammation. Moreover, TAB3 [TGF-β-activated kinase 1 (MAP3K7) binding protein 3] was identified a target m6A methylated RNA immunoprecipitation sequencing sequencing. stability increased through IGF2BP2 (insulin-like growth factor 2 2) its m6A-modified stop codon regions. proinflammatory effects were then explored both vitro vivo. Adeno-associated virus 9 (AAV9)-mediated LPS-induced AKI models. We further Cpd-564 inhibitor that better protective against ischemia/reperfusion-induced than S-adenosyl-l-homocysteine, previously inhibitor. Collectively, promoted enhanced via IGF2BP2-dependent mechanisms. Both genetic pharmacological inhibition inflammation, suggesting METTL3/TAB3 axis potential for treatment AKI.

Language: Английский

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Role of main RNA modifications in cancer: N6-methyladenosine, 5-methylcytosine, and pseudouridine

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 28, 2022

Cancer is one of the major diseases threatening human life and health worldwide. Epigenetic modification refers to heritable changes in genetic material without any nucleic acid sequence results phenotypic changes. modifications regulate many biological processes, such as growth, aging, various diseases, including cancer. With advancement next-generation sequencing technology, role RNA cancer progression has become increasingly prominent a hot spot scientific research. This review studied several common modifications, N6-methyladenosine, 5-methylcytosine, pseudouridine. The deposition roles these coding noncoding RNAs are summarized detail. Based on background, this expression, function, underlying molecular mechanism their regulators further discussed some existing small-molecule inhibitors. More in-depth studies needed broaden understanding epigenetics diagnosis, treatment, prognosis.

Language: Английский

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m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 1, 2023

Abstract N6-methyladenosine (m 6 A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m A writers, erasers, and readers, modulation involved myriad physiological pathological processes. Extensive studies have demonstrated diverse tumours, with effects on tumorigenesis, metastasis, resistance. Recent evidence has revealed an emerging role of tumour immunoregulation, divergent patterns been microenvironment. To depict regulatory immune microenvironment (TIME) its effect evasion, this review focuses TIME, which characterized hypoxia, metabolic reprogramming, acidity, immunosuppression, outlines A-regulated TIME evasion under stimuli. Furthermore, anti-tumour cells are summarized.

Language: Английский

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METTL3: a multifunctional regulator in diseases

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Language: Английский

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PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 15, 2022

Autosomal dominant polycystic kidney disease (ADPKD), among the most common human genetic conditions and a frequent etiology of failure, is primarily caused by heterozygous PKD1 mutations. Kidney cyst formation occurs when dosage falls below critical threshold. However, no framework exists to harness remaining allele or reverse decline. Here, we show that mRNAs produced noninactivated are repressed via their 3'-UTR miR-17 binding element. Eliminating this motif (Pkd1

Language: Английский

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METTL14 promotes prostate tumorigenesis by inhibiting THBS1 via an m6A-YTHDF2-dependent mechanism

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: March 30, 2022

N6-methyladenine (m6A) is the most predominant RNA modification, which has been shown to be related many types of cancers. However, understanding its role in prostate cancer (PCa) largely unknown. Here, we report an upregulation METTL14 that was correlated with poor prognosis PCa patients. Functionally, knocking down inhibited tumor proliferation both vitro and vivo. Mechanically, RNA-seq MeRIP-seq analyses identified THBS1 as downstream target PCa. downregulated expression m6A-dependent manner, resulted recruitment YTHDF2 recognize degrade Thrombospondin 1 (THBS1) mRNA. Thus, our findings revealed acted oncogene by inhibiting via m6A-YTHDF2-dependent manner. could a potential marker therapeutic target.

Language: Английский

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Alkbh1‐mediated DNA N6‐methyladenine modification regulates bone marrow mesenchymal stem cell fate during skeletal aging

Cell Proliferation, Journal Year: 2022, Volume and Issue: 55(2)

Published: Jan. 11, 2022

DNA N6-methyladenine (N6-mA) demethylase Alkbh1 participates in regulating osteogenic differentiation of mesenchymal stem cell (MSCs) and vascular calcification. However, the role bone metabolism remains unclear.Bone marrow cells (BMSCs)-specific knockout mice were used to investigate metabolism. Western blot, qRT-PCR, immunofluorescent staining evaluate expression or optineurin (optn). Micro-CT, histomorphometric analysis, calcein double-labeling assay phenotypes. Cell qRT-PCR adipogenic BMSCs. Dot blotting was detect level N6-mA genomic DNA. Chromatin immunoprecipitation (Chip) assays identify critical targets Alkbh1. adeno-associated virus overexpress aged mice.Alkbh1 BMSCs declined during aging. Knockout promoted while inhibited differentiation. BMSC-specific exhibited reduced mass increased adiposity. Mechanistically, we identified optn as downstream target through which Alkbh1-mediated m6A modification regulated fate. Overexpression attenuated loss fat accumulation mice.Our findings demonstrated that fate bone-fat balance skeletal aging provided a potential for treatment osteoporosis.

Language: Английский

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Targeting the m6A RNA methyltransferase METTL3 attenuates the development of kidney fibrosis

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(2), P. 355 - 369

Published: Feb. 1, 2024

Abstract Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N 6 -methyladenosine (m A) RNA methylation associated with organ fibrosis. We investigated m A profile alterations and the inhibitory effect of in vitro (TGF-β-treated HK-2 cells) vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA or METTL3-specific inhibitor STM2457 vitro. In cells, METTL3 protein levels increased dose- time-dependent manner along an increase cellular levels. UUO model, expression were significantly increased. Transcriptomic profiling demonstrated that epithelial-to-mesenchymal transition- inflammation-related pathways methylation. Genetic pharmacologic inhibition cells decreased TGF-β-induced fibrotic marker expression. STM2457-induced attenuated degree vivo. Furthermore, tissues CKD patients diabetic IgA nephropathy. Therefore, targeting could be potential therapeutic strategy for treating

Language: Английский

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