Acetyltransferase NAT10 promotes an immunosuppressive microenvironment by modulating CD8+ T cell activity in prostate cancer DOI Creative Commons
Liu Ji,

Zhuoran Gu,

Libin Zou

и другие.

Molecular Biomedicine, Год журнала: 2024, Номер 5(1)

Опубликована: Дек. 9, 2024

Abstract N-acetyltransferase 10 (NAT10), an enzyme responsible for ac4C acetylation, is implicated in cancer progression, though its specific biological function prostate remains insufficiently understood. This study clarifies NAT10’s role and effects on the tumor immune microenvironment. NAT10 expression clinical relevance were assessed through bioinformatics, RT-qPCR, IHC analyses, comparing tissues with normal controls. The impact of cell proliferation, migration, invasion was investigated via vitro assays—including CCK-8, EdU, wound healing, 3D-Transwell—as well as vivo mouse xenograft models organoid studies. Further, influence infiltration examined using flow cytometry, IHC, co-culture assays, ELISA to elucidate downstream chemokine effects, specifically targeting CD8 + T cells. Findings indicated significant upregulation cells, enhancing their proliferative invasive capacities. Notably, suppresses recruitment cytotoxicity CCL25/CCR9 axis, fostering immunosuppressive microenvironment that exacerbates progression. An modification score also devised based targets, providing a novel predictive tool evaluating forecasting immunotherapy responses patients cancer. underscores pivotal modulating microenvironment, offering insights into desert phenomenon identifying promising therapeutic target improving efficacy.

Язык: Английский

RNA N4‐acetylcytidine modification and its role in health and diseases DOI Creative Commons
Qiang Wang,

Yixiao Yuan,

Qiang Zhou

и другие.

MedComm, Год журнала: 2025, Номер 6(1)

Опубликована: Янв. 1, 2025

Abstract N4‐acetylcytidine (ac4C) modification is a crucial RNA widely present in eukaryotic RNA. Previous studies have demonstrated that ac4C plays pivotal role viral infections. Despite numerous highlighting the strong correlation between and cancer progression, its detailed roles molecular mechanisms normal physiological processes progression remain incompletely understood. This review first outlines key regulatory enzyme mediating modification, N‐acetyltransferase 10 (NAT10), including critical regulating stability, transcriptional efficiency, translational fidelity. Additionally, it systematically summarizes essential functions of biological processes, stem cell fate determination, spermatogenesis oogenesis, embryonic development, cellular senescence, bone remodeling. Furthermore, this delves into central malignant proliferation, cycle arrest, EMT, drug resistance, death, metabolism, tumor immunotherapy. It also emphasizes potential NAT10 as prognostic biomarker therapeutic target for disease treatment. In summary, clarifies multifaceted both health explores NAT10‐targeted therapies with aim advancing research improving patient outcomes.

Язык: Английский

Процитировано

0
RNA modifications in female reproductive physiology and disease: emerging roles and clinical implications DOI Creative Commons

Yu Xiang,

Hsun‐Ming Chang, Peter C. K. Leung

и другие.

Human Reproduction Update, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Abstract BACKGROUND RNA modifications, collectively known as the epitranscriptome, represent third layer of gene regulation, influencing expression at transcriptional, post-transcriptional, and translational levels. RNA-modifying proteins (RMPs), including writers, erasers, readers, are responsible for depositing, removing, recognizing chemical modifications on molecules. These play a crucial role in linking molecular processes to cellular functions. Over past few decades, growing body laboratory evidence, alongside advances sequencing technologies, has uncovered connections between aberrant reproductive disorders, highlighting their emerging roles female fertility. Given rapid expansion epitranscriptomic research reproduction, comprehensive review is needed summarize broader impacts various rather than focusing individual alone. OBJECTIVE AND RATIONALE This aims elucidate progress understanding biology how dysregulations contribute infertility-related conditions, such polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis. Special focus will be given coding RNAs, particularly those linked fertility supported by solid evidence. The ultimate objective explore targeting RNA-modification machinery can lead development novel therapeutic interventions restoring SEARCH METHODS We conducted thorough peer-reviewed original articles reviews published over two decades using PubMed search engine. Keywords included terms related ‘N6-methyladenosine (m6A)’, ‘N4-acetylcytidine (ac4C)’, ‘adenosine-to-inosine (A–I) editing’, combined with ‘ovary’, ‘oocyte’, ‘embryo’. Additional relevant phrases were also utilized ensure coverage topic. OUTCOMES modification emerged transformative area biology, our epitranscriptome rapidly due significant high-throughput technologies. Regulatory correct deposition functional implementation modifications. Knockout animal models have identified broad, though still incomplete, list involved mammalian processes. include prevalent mRNA, m6A, well A–I editing, and, lesser extent, 5-methylcytosine (m5C) ac4C. regulatory mechanisms impact functions, folliculogenesis, oocyte maturation, fertilization, embryo development. Dysregulation may exacerbate POI, PCOS, Although clinical investigations early stages, show great promise diagnostic biomarkers targets, potential improve health outcomes. WIDER IMPLICATIONS explores relatively underexamined offering significantly advance biology. It underscores relevance disorders identifies biomarkers, RMP-targeted therapies, that could shape future decision-making personalized treatments. insights clinicians embryologists, presenting new avenues diagnosis medicine. REGISTRATION NUMBER N/A.

Язык: Английский

Процитировано

0
NAT10 exacerbates acute renal inflammation by enhancing N4-acetylcytidine modification of the CCL2/CXCL1 axis DOI Creative Commons
Jia-nan Wang,

Xiao‐guo Suo,

Ju-tao Yu

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(17)

Опубликована: Апрель 22, 2025

Inflammation plays an essential role in eliminating microbial pathogens and repairing tissues, while sustained inflammation accelerates kidney damage disease progression. Therefore, understanding the mechanisms of inflammatory response is vital for developing therapies diseases like acute injury (AKI), which currently lacks effective treatment. Here, we identified N-acetyltransferase 10 ( NAT10 ) as important regulator inflammation. , only known “writer” protein N4-acetylcytidine (ac4C) acetylation, elevated renal tubules across various AKI models, human biopsies, cultured tubular epithelial cells (TECs). Conditional knockout (cKO) mouse kidneys attenuates dysfunction, inflammation, infiltration macrophages neutrophils, whereas its conditional knock-in (cKI) exacerbates these effects. Mechanistically, our findings from ac4C-RIP-seq RNA-seq analyses revealed that NAT10-mediated ac4C acetylation enhances mRNA stability a range key chemokines, including C-C motif chemokine ligand 2 CCL2 C-X-C 1( CXCL1 ), promoting macrophage neutrophil recruitment accelerating Additionally, neutralizing antibodies or their receptor inhibitors, abrogated -overexpression TECs -cKI mice. Importantly, inhibiting either through Adeno-associated virus 9 (AAV9)-mediated silencing pharmacologically with found inhibitor Cpd-155, significantly reduces injury. Thus, targeting NAT10/CCL2/CXCL1 axis presents promising therapeutic strategy treating diseases.

Язык: Английский

Процитировано

0
NAT10 mediated Polycystic ovary syndrome through the ac4C modification of CXCL14 DOI
Ding Wang, Hui Li, Lingling Wang

и другие.

The Journal of Steroid Biochemistry and Molecular Biology, Год журнала: 2025, Номер unknown, С. 106767 - 106767

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Qing-Luo-Yin Eased Adjuvant-Induced Arthritis by Inhibiting SIRT1-Controlled Visfatin Production in White Adipose Tissues DOI Creative Commons
Dandan Wang,

Meng-Ke Song,

Qin Yin

и другие.

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 6691 - 6706

Опубликована: Сен. 1, 2024

Nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 regulates both metabolism and immune functions. This study investigated if inhibitory property of herbal formula Qing-Luo-Yin (QLY) contributed to its anti-rheumatic effects.

Язык: Английский

Процитировано

2
Single-Cell Multi-Dimensional data analysis reveals the role of ARL4C in driving rheumatoid arthritis progression and Macrophage polarization dynamics DOI
Ning Tang, Xin Luo, Zhiyu Ding

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 141, С. 112987 - 112987

Опубликована: Авг. 24, 2024

Язык: Английский

Процитировано

1
Acetyltransferase NAT10 promotes an immunosuppressive microenvironment by modulating CD8+ T cell activity in prostate cancer DOI Creative Commons
Liu Ji,

Zhuoran Gu,

Libin Zou

и другие.

Molecular Biomedicine, Год журнала: 2024, Номер 5(1)

Опубликована: Дек. 9, 2024

Abstract N-acetyltransferase 10 (NAT10), an enzyme responsible for ac4C acetylation, is implicated in cancer progression, though its specific biological function prostate remains insufficiently understood. This study clarifies NAT10’s role and effects on the tumor immune microenvironment. NAT10 expression clinical relevance were assessed through bioinformatics, RT-qPCR, IHC analyses, comparing tissues with normal controls. The impact of cell proliferation, migration, invasion was investigated via vitro assays—including CCK-8, EdU, wound healing, 3D-Transwell—as well as vivo mouse xenograft models organoid studies. Further, influence infiltration examined using flow cytometry, IHC, co-culture assays, ELISA to elucidate downstream chemokine effects, specifically targeting CD8 + T cells. Findings indicated significant upregulation cells, enhancing their proliferative invasive capacities. Notably, suppresses recruitment cytotoxicity CCL25/CCR9 axis, fostering immunosuppressive microenvironment that exacerbates progression. An modification score also devised based targets, providing a novel predictive tool evaluating forecasting immunotherapy responses patients cancer. underscores pivotal modulating microenvironment, offering insights into desert phenomenon identifying promising therapeutic target improving efficacy.

Язык: Английский

Процитировано

0