Insights into RNA N6-methyladenosine and programmed cell death in atherosclerosis DOI Creative Commons

Haijiao Long,

Yulu Yu,

Jie Ouyang

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Sept. 3, 2024

Abstract N6-methyladenosine (m 6 A) modification stands out among various RNA modifications as the predominant form within eukaryotic cells, influencing numerous cellular processes implicated in disease development. m A has gained increasing attention development of atherosclerosis and become a research hotspot recent years. Programmed cell death (PCD), encompassing apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, plays pivotal role pathogenesis. In this review, we delve into intricate interplay between diverse PCD pathways, shedding light on their complex association during onset progression atherosclerosis. Clarifying relationship is great significance to provide novel strategies for cardiovascular treatment.

Language: Английский

WTAP/YTHDF1-mediated m6A modification amplifies IFN-γ-induced immunosuppressive properties of human MSCs DOI Creative Commons
Q Chen,

Luoquan Ao,

Qing Zhao

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

The immunosuppressive capacity of mesenchymal stem cells (MSCs) is dependent on the "license" several pro-inflammatory factors to express molecular profiles, which determines therapeutic efficacy MSCs in immune-mediated inflammatory diseases. Of those, interferon-γ (IFN-γ) a key inducer for expression profiles; however, mechanism underlying this effect unknown. To elucidate regulation and biological functions N6-methyladenosine (m6A) modification by IFN-γ-licensing MSCs. Epitranscriptomic microarray analysis MeRIP-qPCR assay were performed identify regulatory WTAP RIP-qPCR, western blot, qRT-PCR RNA stability assays used determine WTAP/m6A/YTHDF1 signaling axis molecules. Further, functional T was tested using flow cytometry, both DSS-induced colitis mice CIA constructed clarify YTHDF1 MSC-mediated immunosuppression. We identified that IFN-γ increased m6A methylation levels molecules, while deficiency abolished IFN-γ-induced promotion modification. activated ERK signaling, induced phosphorylation. Additionally, stabilization post-transcriptionally mRNA molecules (IDO1, PD-L1, ICAM1, VCAM1) an m6A-YTHDF1-dependent manner; further impacted licensing cells. Notably, WTAP/YTHDF1 overexpression enhanced restructures ecology inflammation arthritis models. Our results showed IDO1, VCAM1 mediated WTAP-YTHDF1 involved abilities, shed light enhance clinical potential

Language: Английский

Citations

5
The Emerging, Multifaceted Role of WTAP in Cancer and Cancer Therapeutics DOI Open Access

Guomin Ju,

Jiangchu Lei,

Shuqi Cai

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(11), P. 3053 - 3053

Published: June 4, 2023

Cancer is a grave and persistent illness, with the rates of both its occurrence death toll increasing at an alarming pace. N6-methyladenosine (m6A), most prevalent mRNA modification in eukaryotic organisms, catalyzed by methyltransferases has significant impact on various aspects cancer progression. WT1-associated protein (WTAP) crucial component m6A methyltransferase complex, catalyzing methylation RNA. It been demonstrated to participate numerous cellular pathophysiological processes, including X chromosome inactivation, cell proliferation, cycle regulation, alternative splicing. A better understanding role WTAP may render it reliable factor for early diagnosis prognosis, as well key therapeutic target treatment. found that closely related tumor metabolic autophagy, immunity, ferroptosis, epithelial mesenchymal transformation (EMT), drug resistance. In this review, we will focus latest advances biological functions cancer, explore prospects application clinical therapy.

Language: Английский

Citations

13
The mRNA methyltransferase Mettl3 modulates cytokine mRNA stability and limits functional responses in mast cells DOI Creative Commons
Cristina Leoni, Marian Bataclan, Taku Ito-Kureha

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 29, 2023

Abstract Mast cells are central players in allergy and asthma, their dysregulated responses lead to reduced quality of life life-threatening conditions such as anaphylaxis. The RNA modification N 6 -methyladenosine (m A) has a prominent impact on immune cell functions, but its role mast remains unexplored. Here, by optimizing tools genetically manipulate primary cells, we reveal that the m A mRNA methyltransferase complex modulates proliferation survival. Depletion catalytic component Mettl3 exacerbates effector functions response IgE antigen complexes, both vitro vivo. Mechanistically, deletion or Mettl14, another complex, enhanced expression inflammatory cytokines. By focusing one most affected mRNAs, namely encoding cytokine IL-13, find it is methylated activated affects transcript stability an enzymatic activity-dependent manner, requiring consensus sites Il13 3’-untranslated region. Overall, machinery essential sustain growth restrain responses.

Language: Английский

Citations

13
N6‐methyladenosine‐modified FAM111A‐DT promotes hepatocellular carcinoma growth via epigenetically activating FAM111A DOI Creative Commons
Jian Pu,

Zuoming Xu,

Youguan Huang

et al.

Cancer Science, Journal Year: 2023, Volume and Issue: 114(9), P. 3649 - 3665

Published: July 3, 2023

As an epitranscriptomic modulation manner, N6 -methyladenosine (m6 A) modification plays important roles in various diseases, including hepatocellular carcinoma (HCC). m6 A affects the fate of RNAs. The potential contributions to functions RNA still need further investigation. In this study, we identified long noncoding FAM111A-DT as A-modified and confirmed three sites on FAM111A-DT. level was increased HCC tissues cell lines, correlated with poor survival patients. stability transcript, whose expression showed similar clinical relevance that Functional assays found only promoted cellular proliferation, DNA replication, tumor growth. Mutation abolished Mechanistic investigations bound FAM111A promoter also interacted reader YTHDC1, which recruited histone demethylase KDM3B promoter, leading reduction repressive mark H3K9me2 transcriptional activation FAM111A. positively FAM111A-DT, methyltransferase complex, tissues. Depletion largely attenuated HCC. summary, FAM111A-DT/YTHDC1/KDM3B/FAM111A regulatory axis growth represented a candidate therapeutic target for

Language: Английский

Citations

13
RNA modification-mediated translational control in immune cells DOI Creative Commons

Yu‐Juan Zhang,

Weiguo Hu, Huabing Li

et al.

RNA Biology, Journal Year: 2023, Volume and Issue: 20(1), P. 603 - 613

Published: Aug. 16, 2023

RNA modifications play a vital role in multiple pathways of mRNA metabolism, and translational regulation is essential for immune cells to promptly respond stimuli adapt the microenvironment. N6-methyladenosine (m6A) methylation, which most abundant modification eukaryotes, primarily functions splicing degradation. However, m6Amethylation control its underlying mechanism remain controversial. The m6A methylation translation has received relatively limited attention. In this review, we aim provide comprehensive summary current studies on recent advances understanding regulated by during response. Furthermore, envision possible through may be involved cell function via control.

Language: Английский

Citations

11
METTL3 and METTL14-mediated N6-methyladenosine modification of SREBF2-AS1 facilitates hepatocellular carcinoma progression and sorafenib resistance through DNA demethylation of SREBF2 DOI Creative Commons
Xianjian Wu,

Min Zeng,

Yunyu Wei

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 14, 2024

Abstract As the most prevalent epitranscriptomic modification, N 6 -methyladenosine (m A) shows important roles in a variety of diseases through regulating processing, stability and translation target RNAs. However, potential contributions m A to RNA functions are unclear. Here, we identified functional prognosis-related A-modified SREBF2-AS1 hepatocellular carcinoma (HCC). The expression SREBF2 HCC tissues cells was measured by RT-qPCR. modification level methylated immunoprecipitation assay. progression sorafenib resistance were investigated proliferation, apoptosis, migration, cell viability assays. regulatory mechanisms on Chromatin isolation purification, immunoprecipitation, CUT&RUN, bisulfite DNA sequencing Our findings showed that increased cells, positively correlated with poor survival patients. also prognosis METTL3 METTL14-induced upregulated increasing transcript stability. Functional assays only A-modified, but not non-modified promoted resistance. Mechanistic investigations revealed bound recruited reader FXR1 5-methylcytosine dioxygenase TET1 promoter, leading demethylation at promoter upregulation transcription. rescue critical mediator oncogenic HCC. Together, this study exerted inducing transcriptional activation , suggested as prognostic biomarker therapeutic for

Language: Английский

Citations

4
Regulation of inflammatory diseases via the control of mRNA decay DOI Creative Commons
Masanori Yoshinaga, Osamu Takeuchi

Inflammation and Regeneration, Journal Year: 2024, Volume and Issue: 44(1)

Published: March 15, 2024

Abstract Inflammation orchestrates a finely balanced process crucial for microorganism elimination and tissue injury protection. A multitude of immune non-immune cells, alongside various proinflammatory cytokines chemokines, collectively regulate this response. Central to regulation is post-transcriptional control, governing gene expression at the mRNA level. RNA-binding proteins such as tristetraprolin, Roquin, Regnase family, along with RNA modifications, intricately dictate decay pivotal mediators regulators in inflammatory Dysregulated activity these factors has been implicated numerous human diseases, underscoring significance regulation. The increasing focus on targeting mechanisms presents promising therapeutic strategy autoimmune diseases. This review offers an extensive overview during responses, delving into recent advancements, their implications strides made exploitation.

Language: Английский

Citations

4
YTHDF2 upregulation and subcellular localization dictate CD8 T cell polyfunctionality in anti-tumor immunity DOI Creative Commons
Haiyan Zhang, Xiao-Jing Luo,

Wei Yang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 5, 2024

RNA methylation is an important regulatory process to determine immune cell function but how it affects the anti-tumor activity of CD8 T cells not fully understood. Here we show that N6-methyladenosine (m6A) reader YTHDF2 highly expressed in early effector or effector-like cells. We find facilitates nascent synthesis, and m6A recognition fundamental for this distinctively nuclear protein, which also reinforces its autoregulation at level. Loss exacerbates tumor progression confers unresponsiveness PD-1 blockade mice humans. In addition initiating decay necessary mitochondrial fitness, orchestrates chromatin changes promote polyfunctionality. interacts with IKZF1/3, sustained transcription their target genes. Accordingly, immunotherapy-induced efficacy could be largely restored YTHDF2-deficient through combinational use IKZF1/3 inhibitor lenalidomide a mouse model. Thus, coordinates epi-transcriptional transcriptional networks potentiate immunity, inform therapeutic intervention. has recently identified as mechanism governing functional cellular states, effect on antitumour + explored. authors assign essential nuclear, m6A-recognition-dependent YTHDF2, which, conjunction role IKZF1/3-mediated gene transcription, governs

Language: Английский

Citations

4
The m6A Reader HNRNPC Is a Key Regulator in DSS-Induced Colitis by Modulating Macrophage Phenotype DOI Creative Commons
Xiaohui Fang, Yu Zhang, Ziliang Ke

et al.

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 111812 - 111812

Published: Jan. 16, 2025

Language: Английский

Citations

0
RNA modification: a promising code to unravel the puzzle of autoimmune diseases and CD4+ T cell differentiation DOI Creative Commons
Hui Yu, Zhanchuan Ma,

Sensen Su

et al.

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

Published: March 24, 2025

Dynamic changes in various forms of RNA modification are critical to the functional homeostasis immune system and pathophysiology autoimmune diseases. modification-related proteins play an essential role these processes. At present, research methods diseases mainly detect expression tissues or cells, but there is a lack explorations target RNAs in-depth mechanisms. Considering important CD4 + T cell dysfunction pathogenesis progression diseases, regulatory effect abnormal on cells deserves attention, which will provide perspective for further exploring mechanism In this Review, we discuss patients with highlight effects cells.

Language: Английский

Citations

0