NAT10 promotes vascular remodelling via mRNA ac4C acetylation DOI
Yu Cheng, Yue Chen,

Hao Luo

et al.

European Heart Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Vascular smooth muscle cell (VSMC) phenotype switching is a pathological hallmark in various cardiovascular diseases. N4-acetylcytidine (ac4C) catalyzed by N-acetyltransferase 10 (NAT10) well conserved the enzymatic modification of ribonucleic acid (RNA). NAT10-mediated ac4C acetylation involved physiological and processes, including cardiac remodelling. However, biological functions underlying regulatory mechanisms mRNA modifications vascular diseases remain elusive.

Language: Английский

Nucleic acid drugs: recent progress and future perspectives DOI Creative Commons

Xiaoyi Sun,

Sarra Setrerrahmane,

Chencheng Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 29, 2024

Language: Английский

Citations

13
Base-resolution m5C profiling across the mammalian transcriptome by bisulfite-free enzyme-assisted chemical labeling approach DOI

Liang Lu,

Xiaoting Zhang,

Yuenan Zhou

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(15), P. 2984 - 3000.e8

Published: July 12, 2024

Language: Английский

Citations

11
Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications DOI Creative Commons
Yingying Shi,

Miaoyuan Shi,

Yì Wáng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Language: Английский

Citations

11
M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets DOI Creative Commons
Mengzhen Han,

Qibo Huang,

Xinxin Li

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(4), P. 1238 - 1255

Published: Jan. 1, 2024

RNA modifications play a pivotal role in regulating cellular biology by exerting influence over distribution features and molecular functions at the post-transcriptional level.Among these modifications, N7-methylguanosine (m7G) stands out as one of most prevalent.Over recent years, significant attention has been directed towards understanding implications m7G modification.This modification is present diverse molecules, including transfer RNAs, messenger ribosomal other noncoding RNAs.Its regulation occurs through series specific methyltransferases m7G-binding proteins.Notably, implicated various diseases, prominently across multiple cancer types.Earlier studies have elucidated significance context immune within tumor microenvironment.This comprehensive review culminates synthesis findings related to modulation cells infiltration, encompassing T cells, B innate all orchestrated modification.Furthermore, interplay between its regulatory proteins can profoundly affect efficacy adjuvant therapeutics, thereby potentially serving biomarker therapeutic target for combinatory interventions types.

Language: Английский

Citations

10
Quantification and mapping of RNA modifications DOI
Jun Xiong, Jianyuan Wu, Yu Liu

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 172, P. 117606 - 117606

Published: Feb. 21, 2024

Language: Английский

Citations

9
Accurate Quantification of Ten Methylated Purine Nucleosides by Highly Sensitive and Stable Isotope-Diluted UHPLC–MS/MS DOI
Lyuye Zhang, Weibing Zhang, Hailin Wang

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(28), P. 11366 - 11373

Published: July 6, 2024

The dynamic landscape of cellular nucleotides/nucleosides associated with RNA metabolism, particularly in diseases like cancer, has spurred intensive interest. Here, we report a robust stable isotope-diluted UHPLC-ESI-MS/MS method for accurate quantification 12 purine ribonucleosides, including 10 methylated nucleosides. By the use thermally decomposable ammonium bicarbonate (NH

Language: Английский

Citations

9
N-acetyltransferase 10 impedes EZH2/H3K27me3/GABARAP axis mediated autophagy and facilitates lung cancer tumorigenesis through enhancing SGK2 mRNA acetylation DOI
Nan Xiao, Hongyang Liu, Ruike Zhang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 139823 - 139823

Published: Jan. 1, 2025

Language: Английский

Citations

1
Glucose homeostasis controls N-acetyltransferase 10-mediated ac4C modification of HK2 to drive gastric tumorigenesis DOI Creative Commons
Qiang Wang, Mengmeng Li, Chen Chen

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(6), P. 2428 - 2450

Published: Jan. 20, 2025

Rationale: Abnormal metabolic states contribute to a variety of diseases, including cancer. RNA modifications have diverse biological functions and are implicated in cancer development, gastric (GC). However, the direct relationship between glucose homeostasis 4-acetylcytosine (ac4C) modification GC remains unclear. Methods: The prognostic value acetyltransferase NAT10 expression was evaluated human cohort. Additionally, preoperative PET/CT data from patients Micro-PET/CT imaging mice were employed assess metabolism. role investigated through various experiments, xenografts, organoids, conditional knockout (cKO) mouse model. underlying mechanisms examined using dot blotting, immunofluorescence staining, co-immunoprecipitation, high-throughput sequencing, among other techniques. Results: Glucose deprivation activates autophagy-lysosome pathway, leading degradation by enhancing its interaction with sequestosome 1 (SQSTM1)/microtubule-associated protein light chain 3 alpha (LC3) complex, ultimately resulting reduction ac4C modification. Furthermore, levels elevated tissues correlate poor prognosis. A strong correlation exists 18F-FDG uptake patients. drives glycolytic metabolism carcinogenesis vitro vivo. Mechanistically, stimulates at intersection coding sequence (CDS) 3' untranslated region (3'UTR) hexokinase 2 (HK2) mRNA, stability activating thereby driving tumorigenesis. Conclusion: Our findings highlight critical crosstalk epitranscriptome carcinogenesis. This finding offers potential strategy targeting NAT10/HK2 axis for treatment patients, especially those highly active

Language: Английский

Citations

1
Interplay of m6A RNA methylation and gut microbiota in modulating gut injury DOI Creative Commons
Haixia Wang, Juanjuan Han, Xinan Zhang

et al.

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 17, 2025

The gut microbiota undergoes continuous variations among individuals and across their lifespan, shaped by diverse factors encompassing diet, age, lifestyle choices, medication intake, disease states. These microbial inhabitants play a pivotal role in orchestrating physiological metabolic pathways through the production of metabolites like bile acids, choline, short-chain fatty neurotransmitters, thereby establishing dynamic "gut-organ axis" with host. intricate interplay between host is indispensable for health, RNA N6-methyladenosine modification, epigenetic mark on RNA, emerges as key player this process. M6A most prevalent internal modification eukaryotic has garnered significant attention realm epigenetics. Recent findings underscore its potential to influence diversity intestinal barrier function modulating gene expression patterns. Conversely, microbiota, impact landscape cells, may indirectly regulate recruitment activity m6A-modifying enzymes. This review endeavors delve into biological functions m6A consequences injury pathogenesis, elucidating partial possible mechanisms which maintain health homeostasis. Furthermore, it also explores crosstalk them injury, offering novel perspective that deepens our understanding underlying diseases.

Language: Английский

Citations

1
Targeting the epigenome to reinvigorate T cells for cancer immunotherapy DOI Creative Commons

Dian Xiong,

Lu Zhang, Zhi‐Jun Sun

et al.

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Dec. 4, 2023

Abstract Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) has revolutionized the field of cancer treatment; however, ICI efficacy is constrained by progressive dysfunction CD8 + tumor-infiltrating lymphocytes (TILs), which termed T cell exhaustion. This process driven diverse extrinsic factors across heterogeneous tumor immune microenvironment (TIME). Simultaneously, tumorigenesis entails robust reshaping epigenetic landscape, potentially instigating In this review, we summarize mechanisms governing microenvironmental cues leading to exhaustion, and discuss therapeutic potential targeting regulators for immunotherapies. Finally, outline conceptual technical advances in developing treatment paradigms involving immunostimulatory agents therapies.

Language: Английский

Citations

21