RNA N6‐Methyladenosine‐Binding Protein YTHDFs Redundantly Attenuate Cancer Immunity by Downregulating IFN‐γ Signaling in Gastric Cancer DOI Creative Commons

Dongjun Jang,

Chanwoong Hwa, Seoyeon Kim

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Abstract Immunotherapy holds potential as a treatment for gastric cancer (GC), though immune checkpoint inhibitor (ICI) resistance remains an obstacle. One mechanism involves defects in interferon‐γ (IFN‐γ) signaling, which IFN‐γ is linked to improved responsiveness ICIs. Herein, the roles of RNA N 6 ‐methyladenosine (m6A) modifications regulation signaling and ICIs are unveiled. The m6A‐binding protein YTH RNA‐binding F1 (YTHDF1) overexpressed GC tissues, correlating with suppression immunity poorer survival rates. YTHDF1 overexpression impaired cells, knockdown studies indicated redundant effects YTHDF2 YTHDF3 responsiveness. immunoprecipitation sequencing revealed YTHDFs directly target interferon regulatory factor 1 (IRF1) mRNA, master regulator leading reduced stability consequent downregulation signaling. Furthermore, mouse syngeneic tumor models, Ythdf1 depletion cells resulted growth increased tumor‐infiltrating lymphocytes, attributed augmentation Collectively, these findings highlight how modulate by influencing through IRF1 regulation, suggesting their viability therapeutic targets immunotherapy.

Language: Английский

Optimizing therapeutic outcomes: preconditioning strategies for MSC-derived extracellular vesicles DOI Creative Commons
Yuqi Song, Fuxin Liang, Weidong Tian

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 10, 2025

Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) are increasingly recognized for their therapeutic potential in regenerative medicine, driven by capabilities immunomodulation tissue repair. However, MSCs present risks such as immunogenic responses, malignant transformation, the to transmit infectious pathogens due intrinsic proliferative differentiative abilities. In contrast, MSC-EVs, particularly exosomes (MSC-exosomes, 30–150 nm diameter), offer a safer profile. These acellular mitigate associated with immune rejection tumorigenesis inherently incapable of forming ectopic tissues, thereby enhancing clinical safety applicability. This review highlights promise MSC-exosomes especially focusing on modulation miRNA (one bioactive molecules MSC-EVs) profiles through various preconditioning strategies exposure hypoxia, chemotherapeutic agents, inflammatory cytokines, physical stimuli. Such conditioning is shown optimize potential. Key miRNAs including miR-21, miR-146, miR-125a, miR-126, miR-181a noted roles facilitating repair modulating responses. functionalities position valuable tool personalized case exosome-based interventions. Despite this also acknowledged limitations traditional MSC therapies advocates strategic pivot towards modalities enhance outcomes. By discussing recent advances detail identifying remaining pitfalls, aims guide future directions improving efficacy MSC-exosome-based therapeutics. Additionally, variability MSC-EVs presents challenges diverse play regulating gene expression cell behavior. The content can be influenced differences isolation purification methods, which may alter specific miRNAs, contributing effects.

Language: Английский

Citations

3
Post‐Translational Modifications of RNA‐Modifying Proteins in Cellular Dynamics and Disease Progression DOI Creative Commons
Yunfan Lin, Pei Lin, Ye Lu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(44)

Published: Oct. 8, 2024

Abstract RNA‐modifying proteins, classified as “writers,” “erasers,” and “readers,” dynamically modulate RNA by adding, removing, or interpreting chemical groups, thereby influencing stability, functionality, interactions. To date, over 170 distinct modifications more than 100 enzymes have been identified, with ongoing research expanding these numbers. Although significant progress has made in understanding modification, the regulatory mechanisms that govern proteins themselves remain insufficiently explored. Post‐translational (PTMs) such phosphorylation, ubiquitination, acetylation are crucial modulating function behavior of proteins. However, full extent PTM influence on their role disease development remains to be fully elucidated. This review addresses gaps offering a comprehensive analysis roles PTMs play regulating Mechanistic insights provided into how alter biological processes, contribute cellular function, drive progression. In addition, current landscape is examined, highlighting therapeutic potential targeting for precision medicine. By advancing networks, this seeks facilitate effective strategies inspire future critical area

Language: Английский

Citations

4
Pharmacology of Epitranscriptomic Modifications: Decoding the Therapeutic Potential of RNA Modifications in Drug Resistance DOI
Abdullah Alkhammash

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 994, P. 177397 - 177397

Published: Feb. 18, 2025

Language: Английский

Citations

0
Increased Alleviation of Bone Destruction in Individuals with Rheumatoid Arthritis via the Coinhibition of the METTL3 and YTHDF1 Axis by the Combination of Triptolide and Medicarpin DOI Creative Commons
Yi Jiao, Zhaoran Wang,

Wenya Diao

et al.

Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
RNA N6‐Methyladenosine‐Binding Protein YTHDFs Redundantly Attenuate Cancer Immunity by Downregulating IFN‐γ Signaling in Gastric Cancer DOI Creative Commons

Dongjun Jang,

Chanwoong Hwa, Seoyeon Kim

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Abstract Immunotherapy holds potential as a treatment for gastric cancer (GC), though immune checkpoint inhibitor (ICI) resistance remains an obstacle. One mechanism involves defects in interferon‐γ (IFN‐γ) signaling, which IFN‐γ is linked to improved responsiveness ICIs. Herein, the roles of RNA N 6 ‐methyladenosine (m6A) modifications regulation signaling and ICIs are unveiled. The m6A‐binding protein YTH RNA‐binding F1 (YTHDF1) overexpressed GC tissues, correlating with suppression immunity poorer survival rates. YTHDF1 overexpression impaired cells, knockdown studies indicated redundant effects YTHDF2 YTHDF3 responsiveness. immunoprecipitation sequencing revealed YTHDFs directly target interferon regulatory factor 1 (IRF1) mRNA, master regulator leading reduced stability consequent downregulation signaling. Furthermore, mouse syngeneic tumor models, Ythdf1 depletion cells resulted growth increased tumor‐infiltrating lymphocytes, attributed augmentation Collectively, these findings highlight how modulate by influencing through IRF1 regulation, suggesting their viability therapeutic targets immunotherapy.

Language: Английский

Citations

0