Combating cancer stem cells: RNA m6A methylation and small-molecule drug discovery DOI Creative Commons
Honghai Zhang, Xueer Wang, Jianjun Chen

et al.

Frontiers in Drug Discovery, Journal Year: 2024, Volume and Issue: 4

Published: Sept. 30, 2024

Cancer stem cells (CSCs) are a small population of less differentiated with robust self-renewal ability. CSCs have been recognized as the root cause tumor initiation, progression, relapse, and drug resistance. Recent studies from us others highlighted that N 6 -methyladenosine (m A), most prevalent modification in mRNA, plays crucial role carcinogenesis CSC homeostasis. Dysregulation m A machinery has implicated survival self-renewal, thereby regulating cancer progression therapeutic In this review, we provide an overview roles molecular mechanisms RNA self-renewal. Additionally, summarize currently known small-molecule inhibitors targeting dysregulated discuss proof-of-concept focusing on efficacy these compounds eliminating cancers.

Language: Английский

Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets DOI Creative Commons

Fan Guan,

Ruixuan Wang,

Zhenjie Yi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

Citations

3
Disrupting EDEM3‐induced M2‐like macrophage trafficking by glucose restriction overcomes resistance to PD‐1/PD‐L1 blockade DOI Creative Commons
Shaoyong Peng, Minhao Wu,

Yan Qian

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Immunotherapy is beneficial for some colorectal cancer (CRC) patients, but immunosuppressive networks limit its effectiveness. Cancer-associatedfibroblasts (CAFs) are significant in immune escape and resistance toimmunotherapy, emphasizing the urgent need new treatment strategies. Flow cytometric, Western blotting, proteomics analysis, analysis of public database data, genetically modified cell line models, T coculture, crystal violetstaining, ELISA, metabonomic clinical tumour samples were conducted to assess role EDEM3 itsmolecular mechanisms. We evaluated theeffects FMD plus 2-DG on antitumour immunity using multipleximmunofluorescence, flow cytometry, cytokine profiling, TUNEL assays, xenografttumours, vivo studies. show thatCAFs upregulate PD-L1 glycosylation contribute evasion byglycosyltransferase EDEM3. Additionally, plays a immunityduring progression. However, EDEM3-mediated upregulation expression underpins PD-1/PD-L1 blockade vivo. This finding contradictsthe previous trend that positive indicates strong responseto blockade. Mechanistically, high-EDEM3 facilitates M2-like blockade.Mechanistically, polarizationand chemotactic migration macrophages, which enriched theperipheral region tumours compared thecore region, precluding access CD8+ cells tumourfoci. Furthermore, we predominantly activates recruited macrophagesvia glucose metabolism-dependent mechanism. Manipulationof utilization by fasting-mimicking diet(FMD) treatmentsynergistically with PD-1 antibody elicits potent activity byeffectively decreasing glycosylated expression, augmenting CD8+effector infiltration activation while concurrently reducing infiltration.TheCAFs-EDEM3-M2-like macrophage axis critical promotingimmunotherapy resistance. Our study suggests blocking EDEM3-induced macro phage trafficking promising effective strategy overcomeresistance checkpoint therapy offeringhope improved outcomes. Cancer-associated fibroblasts can enhance through glycosyltransferase EDEM3, contributing during recruit macrophages via Blocking antagonizes recruiting polarizing synergistically improve anticancer immunity.

Language: Английский

Citations

1
Spermine synthase engages in macrophages M2 polarization to sabotage antitumor immunity in hepatocellular carcinoma DOI
Yining Sun, Peitao Zhou,

Junying Qian

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Language: Английский

Citations

4
Epitranscriptomics in the Glioma Context: A Brief Overview DOI Open Access
Pablo Santamarina‐Ojeda, Agustín F. Fernández, Mario F. Fraga

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 578 - 578

Published: Feb. 8, 2025

Epitranscriptomics, the study of chemical modifications in RNA, has emerged as a crucial field cellular regulation, adding another layer to established landscape DNA- and histone-based epigenetics. A wide range RNA modifications, including N6-methyladenosine, pseudouridine, inosine, have been identified across nearly all species, influencing essential processes such transcription, splicing, stability, translation. In context brain tumors, particularly gliomas, specific epitranscriptomic signatures reported play role tumorigenesis. Despite growing evidence, biological implications various remain poorly understood. This review offers an examination main interplay between modified unmodified molecules, how they could contribute glioma-like phenotypes, therapeutic impact targeting these mechanisms.

Language: Английский

Citations

0
Targeting YTHDF2 impacts the epitranscriptome and overcomes tumor therapy resistance DOI
Zhicong Zhao, Li Han, Qiwei Ge

et al.

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
The m6A revolution: transforming tumor immunity and enhancing immunotherapy outcomes DOI Creative Commons
Tongguo Shi, Huan Zhang, Yueqiu Chen

et al.

Cell & Bioscience, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 22, 2025

Abstract N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, plays a critical role development and progression of various diseases, including cancer, through its regulation degradation, stabilization, splicing, cap-independent translation. Emerging evidence underscores significant m6A modifications both pro-tumorigenic anti-tumorigenic immune responses. In this review, we provide comprehensive overview examine relationship between regulators cancer Additionally, summarize recent advances understanding how influence tumor responses by directly modulating cells (e.g., dendritic cells, tumor-associated macrophages, T cells) indirectly affecting via mechanisms such as cytokine chemokine regulation, modulation cell surface molecules, metabolic reprogramming. Furthermore, explore potential synergistic effects targeting combination with checkpoint inhibitor (ICI) therapies. Together, review consolidates current knowledge on m6A-mediated immunity, offering insights into deeper these may identify patients who are likely to benefit from immunotherapies.

Language: Английский

Citations

0
The role of YTHDF2 in anti-tumor immunity DOI Creative Commons
Leying Zhang, Cunte Chen, Jia Feng

et al.

Cell investigation., Journal Year: 2025, Volume and Issue: 1(1), P. 100008 - 100008

Published: Feb. 26, 2025

Language: Английский

Citations

0
Mechanism of FBXW7 mRNA degradation mediated by circSMAD2 through METTL3-METTL14 m6A axis affects proliferation and invasion of endometrial stromal cells DOI
Peng Yuan, P. Wang,

Yuanmei Lou

et al.

Journal of Reproductive Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 104523 - 104523

Published: March 1, 2025

Language: Английский

Citations

0
Orchestration of immunoregulatory signaling ligand and receptor dynamics by mRNA modifications: Implications for therapeutic potential DOI

Zizhao Mai,

Xu Chen, Ye Lu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142987 - 142987

Published: April 1, 2025

Language: Английский

Citations

0
RNA modifications in cancer immune therapy: regulators of immune cells and immune checkpoints DOI Creative Commons

Xiangyu Qin,

Huali Liu, Qixuan Zhang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 20, 2024

RNA modifications are epigenetic changes that alter the structure and function of molecules, playing a crucial role in onset, progression, treatment cancer. Immune checkpoint inhibitor (ICI) therapies, particularly PD-1 blockade anti-CTLA-4 treatments, have changed landscape virous cancers, showing great potential different cancer patients, but sensitivity to these therapies is limited certain individuals. This review offers comprehensive survey functions therapeutic implications four principal modifications, highlighting significance m6A realms immune cells tumor immunotherapy. starts by providing foundational summary roles assume within cell community, focusing on T cells, NK macrophages, dendritic cells. We then discuss how influence intricate regulatory mechanisms governing expression, modulation ICI efficacy, prediction outcomes, drug targeting genes regulated modifications. Finally, we explore gene editing, vaccines, adoptive offering valuable insights into use

Language: Английский

Citations

2