YTHDF2 upregulation and relocation dictate CD8 T cell polyfunctionality in tumor immunity DOI
Haiyan Zhang, Xiao-Jing Luo,

Wei Yang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Abstract Epigenetic traits impact the antitumor function of CD8 T cells, yet whether and how RNA methylation programs engage in cell immunity is poorly understood. Here we show that N 6 -methyladenosine (m A) reader YTHDF2 highly expressed early effector or effector-like cells partially distributed nucleus. loss exacerbates tumor progression confers unresponsiveness to PD-1 blockade mice humans. In addition initiating decay for mitochondrial fitness, can orchestrate chromatin regulation promote polyfunctionality. YTHDF2-mediatd preservation gene transcription arises from interaction with IKZF1/3. Accordingly, immunotherapy-induced efficacy could be largely restored YTHDF2-deficient through combinational use lenalidomide. Moreover, m A recognition fundamental translocation nucleus autoregulation at level. Thus, coordinates epitranscriptional transcriptional networks potentiate immunity. Highlights expression distribution underpin threshold bona fide response Canonical YTHDF2-mRNA pathway alleviates stress exhaustion Nuclear sequesters IKZF1/3-mediated repression safeguard polyfunctionality The tumoricidal activity repaired synergy anti-PD-1 lenalidomide

Language: Английский

Biological functions of 5-methylcytosine RNA-binding proteins and their potential mechanisms in human cancers DOI Creative Commons
Tingting Zhao, Zhe Zhang, Zhuo Chen

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 7, 2025

The 5-methylcytosine (m5C) modification is a crucial epigenetic RNA modification, which involved in the post-transcriptional regulation of genes. It plays an important role various biological processes, including cell metabolism, growth, apoptosis, and tumorigenesis. By affecting proliferation, migration, invasion, drug sensitivity tumor cells, m5C methylation vital part initiation progression tumors closely associated with poor prognosis. m5C-related proteins are categorized into three functional groups: methyltransferases (m5C writers), demethylases erasers), methyl-binding readers). This paper introduces several common methodologies for detecting methylation; reviews molecular structure functions readers, ALYREF, YBX1, YBX2, RAD52, YTHDF2, FMRP, SRSF2. further summarizes their roles regulatory mechanisms tumors, offering novel targets insights treatment.

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

YTHDF2: a key RNA reader and antitumor target DOI

Sai Jin Xiao,

Songqi Duan, Michael A. Caligiuri

et al.

Trends in Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0

Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD DOI Creative Commons

Moeka Nakashima,

Naoko Suga,

Yuka Ikeda

et al.

Non-Coding RNA, Journal Year: 2024, Volume and Issue: 10(1), P. 11 - 11

Published: Feb. 5, 2024

Noncoding RNAs (ncRNAs), including circular (circRNAs) and N6-methyladenosine (m6A), have been shown to play a critical role in the development of various diseases obesity metabolic disorder-associated fatty liver disease (MAFLD). Obesity is chronic caused by excessive fat accumulation body, which has recently become more prevalent foremost risk factor for MAFLD. Causes may involve interaction genetic, behavioral, social factors. m6A RNA methylation might add novel inspiration understanding MAFLD with post-transcriptional regulation gene expression. In particular, circRNAs, microRNAs (miRNAs), be implicated progression Interestingly, modification can modulate translation, degradation, other functions ncRNAs. miRNAs/circRNAs also modifications affecting writers, erasers, readers. turn, ncRNAs could expression regulators different ways. However, there limited evidence on how these interact affect promotion diseases. It seems that occur DNA, RNA, proteins associated several biological properties. This study provides mechanistic association diseases, especially Comprehension between contribute treatment tactics

Language: Английский

Citations

3

Elevated WTAP promotes hyperinflammation by increasing m6A modification in inflammatory disease models DOI Creative Commons
Yong Ge, Rong Chen,

Tao Ling

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(14)

Published: May 16, 2024

Emerging evidence has linked the dysregulation of N6-methyladenosine (m6A) modification to inflammation and inflammatory diseases, but underlying mechanism still needs investigation. Here, we found that high levels m6A in a variety hyperinflammatory states are p65-dependent because Wilms tumor 1–associated protein (WTAP), key component "writer" complex, is transcriptionally regulated by p65, its overexpression can lead increased modification. Mechanistically, upregulated WTAP more prone phase separation facilitate aggregation writer complex nuclear speckles deposition marks on active transcripts, thereby accelerating proinflammatory response. Further, myeloid deficiency attenuates severity LPS-induced sepsis DSS-induced IBD. Thus, effect general risk-increasing mechanism, interrupting assembly reduce global targeting may be potential promising therapeutic strategy for alleviating hyperinflammation.

Language: Английский

Citations

3

Transcription factor RELA promotes hepatocellular carcinoma progression by promoting the transcription of m6A modulator METTL3 DOI
Jian Wu, Weixing Wang, Yongbin Zheng

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 255, P. 155168 - 155168

Published: Feb. 2, 2024

Language: Английский

Citations

2

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

The potential of RNA methylation in the treatment of cardiovascular diseases DOI Creative Commons
Kai Wang, Yuqin Wang, Yinghui Li

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(8), P. 110524 - 110524

Published: July 20, 2024

RNA methylation has emerged as a dynamic regulatory mechanism that impacts gene expression and protein synthesis. Among the known modifications, N6-methyladenosine (m

Language: Английский

Citations

2

Regulation and application of m6A modification in tumor immunity DOI
Qunli Xiong, Yaguang Zhang, Zheng Ying

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 6, 2024

Language: Английский

Citations

2

The physiological and pathological roles of RNA modifications in T cells DOI

Yu Deng,

Jing Zhou, Huabing Li

et al.

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(9), P. 1578 - 1592

Published: July 9, 2024

Language: Английский

Citations

1