N6-methyladenosine RNA methylation, a new hallmark of metabolic reprogramming in the immune microenvironment DOI Creative Commons
Xiaoyue Li,

Lin Peng,

Xuelian Yang

et al.

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

Published: Dec. 20, 2024

N6-methyladenosine is one of the most common and reversible post-transcriptional modifications in eukaryotes, it involved alternative splicing RNA transcription, degradation, translation. It well known that cancer cells acquire energy through metabolic reprogramming to exhibit various biological behaviors. Moreover, numerous studies have demonstrated m6A induces by regulating expression core genes or activating signaling pathways. Meanwhile, related regulators are key targets regulation immune effects. We further summarize how contribute tumor metabolism, these events affect microenvironment, with a specific focus on different cell types. Finally, we applications this field immunotherapy. review potential role microenvironment its regulatory mechanism, aim providing new for

Language: Английский

m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism DOI Creative Commons
Shiwei Yue, Hailing Liu,

Hong-Fei Su

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 15, 2023

Abstract Glycolytic reprogramming is one of the most important features cancer and plays an integral role in progression cancer. In cells, changes glucose metabolism meet needs self-proliferation, angiogenesis lymphangiogenesis, metastasis, also affect immune escape, prognosis evaluation therapeutic effect The n6-methyladenosine (m6A) modification RNA widespread eukaryotic cells. Dynamic reversible m6A modifications are widely involved regulation stem cell renewal differentiation, tumor therapy resistance, microenvironment, metabolism. Lately, more evidences show that can glycolysis process tumors a variety ways to regulate biological behavior tumors. this review, we discussed genesis development, elaborated detail profound impact on different by regulating glycolysis. We believe modified has great significance potential for treatment.

Language: Английский

Citations

47
RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy DOI Creative Commons
Weiwei Liu,

Si-Qing Zheng,

Li Tian

et al.

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

Published: March 27, 2024

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding pathophysiology, inspiring development therapeutics. As a crucial component epigenetics at post-transcription level, RNA modification significantly determines fates, further affecting various biological processes cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells different stages immunological contexts. In this review, we characterize distribution features, modifying mechanisms functions 8 modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively most studied types. Then regulatory roles these diverse health disease contexts comprehensively described, categorized as glucose, lipid, amino acid, mitochondrial metabolism. And highlight regulation modifications immunometabolism, influencing responses. Above all, provide thorough discussion about clinical implications metabolism-targeted therapy immunotherapy, progression modification-targeted agents, its potential RNA-targeted Eventually, give legitimate perspectives for future researches field from methodological requirements, mechanistic insights, to therapeutic applications.

Language: Английский

Citations

34
Deciphering the interplay between SETD2 mediated H3K36me3 and RNA N6-methyladenosine in clear cell renal cell carcinoma (ccRCC) DOI Creative Commons

Shafiq Shaikh,

Xia Zhao, Ryan T. Wagner

et al.

Epigenetics, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 28, 2025

RNA N6-methyladenosine (m6A) plays diverse roles in metabolism and its deregulation contributes to tumor initiation progression. Clear cell renal carcinoma (ccRCC) is characterized by near ubiquitous loss of VHL followed mutations epigenetic regulators PBRM1, SETD2, BAP1. Mutations a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, metabolic reprogramming. While m6A H3K36me3 separately implicated tumorigenesis, may participate directly targeting, but the m6A-H3K36me3 interplay has not been investigated context ccRCC. Using RCC-relevant SETD2 isogenic knockout rescue line models, we demonstrate dynamic redistribution depleted transcriptome, subset transcripts involved reprogramming demonstrating dependent expression level changes. panel six modifications show that redistributes regions enriched gained active enhancers upon inactivation. Finally, reversal transcriptomic programs mediated reprogramming, viability through pharmacologic inhibition or genetic ablation writer METTL3 specific deficient cells. Thus, targeting represent novel therapeutic vulnerability mutant

Language: Английский

Citations

1
The role of RNA-modifying proteins in renal cell carcinoma DOI Creative Commons
Muna A. Ali, Khuloud Bajbouj, Iman M. Talaat

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(3)

Published: March 19, 2024

Abstract Gene expression is one of the most critical cellular processes. It controlled by complex mechanisms at genomic, epigenomic, transcriptomic, and proteomic levels. Any aberration in these can lead to dysregulated gene expression. One recently discovered process that controls includes chemical modifications RNA molecules RNA-modifying proteins, a field known as epitranscriptomics. Epitranscriptomics regulate mRNA splicing, nuclear export, stabilization, translation, or induce degradation target molecules. Dysregulation proteins has been found contribute many pathological conditions, such cancer, diabetes, obesity, cardiovascular diseases, neurological among others. This article reviews role epitranscriptomics pathogenesis progression renal cell carcinoma. summarizes molecular function

Language: Английский

Citations

5
N6-methyladenosine (m6A) methylation in kidney diseases: Mechanisms and therapeutic potential DOI Creative Commons
Yuting Sun, De Jin, Ziwei Zhang

et al.

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Journal Year: 2023, Volume and Issue: 1866(4), P. 194967 - 194967

Published: Aug. 6, 2023

The N6-methyladenosine (m6A) modification is regulated by methylases, commonly referred to as "writers," and demethylases, known "erasers," leading a dynamic reversible process. Changes in m6A levels have been implicated wide range of cellular processes, including nuclear RNA export, mRNA metabolism, protein translation, splicing, establishing strong correlation with various diseases. Both physiologically pathologically, methylation plays critical role the initiation progression kidney disease. may also facilitate early diagnosis treatment diseases, according accumulating research. This review aims provide comprehensive overview potential mechanism well its application such There will be thorough examination mechanisms, paying particular attention interplay between writers, erasers, readers. Furthermore, this paper elucidate diseases methylation, summarize expression patterns pathological tissues, discuss therapeutic benefits targeting context

Language: Английский

Citations

10
FTO-associated osteoclastogenesis promotes alveolar bone resorption in apical periodontitis male rat via the HK1/USP14/RANK pathway DOI Creative Commons

Yajie Qian,

Jing Wu, Weidong Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 11, 2025

Alveolar bone resorption (ABR) is a key pathological manifestation in the development of apical periodontitis (AP) and contributes to AP-associated tooth loss among AP patients clinic. However, underlying mechanism ABR largely unknown. Here we show, total levels N6-methyladenosine (m6A) were reduced male rat alveolar tissues BMDM-derived osteoclasts (OC), which was associated with up-regulation obesity-associated protein (FTO). Subsequently FTO-mediated hexokinase (HK1) demethylation modification enhancing glycolytic pathway that stabilizes receptor activator NF-κB (RANK) via deubiquitination activity ubiquitin-specific protease 14 (USP14), further promotes osteoclastogenesis participate AP-related development. Finally, Dac51 (an FTO inhibitor) 2-DG HK1 both exhibit inhibitory osteoclastogenesis. Our current study reveals molecular on osteoclastogenesis-related provides therapeutic target modulating FTO/HK1/USP14/RANK axis. loss, whose Here, authors show

Language: Английский

Citations

0
The biological roles and molecular mechanisms of m6A reader IGF2BP1 in the hallmarks of cancer DOI Creative Commons

Qiu Li,

Shourong Wu, Lei Zhang

et al.

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101567 - 101567

Published: Feb. 1, 2025

Language: Английский

Citations

0
Functions of N6-methyladenosine in cancer metabolism: from mechanism to targeted therapy DOI Creative Commons

Jiayi He,

Furong Liu, Zhanguo Zhang

et al.

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: April 13, 2023

Abstract N6-methyladenosine (m6A) is the most abundant modification of eukaryotic mRNA and involved in almost every stage RNA metabolism. The m6A on has been demonstrated to be a regulator occurrence development substantial number diseases, especially cancers. Increasing evidence shown that metabolic reprogramming hallmark cancer crucial for maintaining homeostasis malignant tumors. Cancer cells rely altered pathways support their growth, proliferation, invasion metastasis an extreme microenvironment. regulates mainly by either directly acting enzymes transporters or indirectly influencing metabolism-related molecules. This review discusses functions RNAs, its role cell pathways, possible underlying mechanisms effects implication this therapy.

Language: Английский

Citations

7
METTL3 and IGF2BP1-mediated m6A modification of ZHX2 promotes tumor property of renal cell carcinoma DOI Creative Commons
Bangming Xiao, Yalan Li, Yong Yang

et al.

Kidney & Blood Pressure Research, Journal Year: 2024, Volume and Issue: 49(1), P. 787 - 798

Published: Aug. 19, 2024

Introduction: Renal cell carcinoma (RCC) is a common type of kidney cancer with limited treatment options and high mortality rate. Therefore, it essential to understand the role mechanism key genes in RCC development progression. This study aimed analyze zinc fingers homeoboxes 2 (ZHX2) underlying mechanism. Methods: RNA expression was analyzed by quantitative real-time polymerase chain reaction, while protein Western blotting assay immunohistochemistry assay. Cell viability evaluated using CCK-8 assay, proliferation assessed EdU The rate apoptosis quantified flow cytometry. Transwell assays were conducted migration invasion. sphere formation performed assess microspheres. Additionally, m6A immunoprecipitation utilized investigate relationship between ZHX2 two proteins, methyltransferase like 3 (METTL3) insulin-like growth factor mRNA-binding 1 (IGF2BP1). stability mRNA through Actinomycin D Furthermore, xenograft mouse model effect overexpression METTL3 silencing on tumor properties vivo. Results: upregulated both tissues cells when compared healthy renal human cortex proximal convoluted tubule epithelial cells. Depletion inhibited proliferation, migration, invasion, spheroid-forming capacity but promoted apoptosis. Moreover, found that METTL3-mediated methylation IGF2BP1 also stabilized modification. showed potential for attenuating effects induced counteracted inhibitory depletion Conclusion: IGF2BP1-mediated modification finding suggests may serve as therapeutic target RCC, providing valuable insights future clinical interventions.

Language: Английский

Citations

2
SOX11 as a prognostic biomarker linked to m6A modification and immune infiltration in renal clear cell carcinoma DOI Open Access

Kaihong Wang,

Xinpeng Chen, Yifu Liu

et al.

Translational Cancer Research, Journal Year: 2024, Volume and Issue: 13(7), P. 3536 - 3555

Published: July 1, 2024

The prognosis for patients with kidney renal clear cell carcinoma (KIRC) remains unfavorable, and the understanding of SRY-box transcription factor 11 (SOX11) in KIRC is still limited. purpose this paper to explore role SOX11 KIRC.

Language: Английский

Citations

1