METTL14 promotes neuroblastoma by inhibiting YWHAH via an m6A-YTHDF1-dependent mechanism DOI Creative Commons
Jian Pan, Jianwei Wang, Hongli Yin

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 28, 2023

Abstract Neuroblastoma (NB) is a widely recognized childhood tumor with high global incidence. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has gained significant attention, and the impact methyltransferase-like 14 (METTL14) on progression been extensively investigated various cancer types. Nevertheless, precise influence METTL14 NB remains unexplored. Based data obtained from Target database, our study revealed upregulation high-risk patients, which exhibited strong correlation poor prognosis. Additionally, we identified ETS1 YY1 as upstream regulators METTL14, exerting control over its expression. In vitro experiments involving knockdown cells demonstrated substantial inhibition cell proliferation, migration, invasion. Moreover, suppression also resulted tumorigenesis nude mouse models. Through MeRIP-seq RNA-seq analyses, further discovered that YWHAH downstream METTL14. Mechanistically, observed methylated transcripts, particularly 5'UTR region, were specifically by m6A "reader" protein, YTHDF1, promoted degradation mRNA. Furthermore, downregulation led to activation PI3K/AKT signaling pathway, thereby facilitating activity neuroblastoma cells. Collectively, findings have provided valuable insights into oncogenic effects cells, highlighting through an m6A-YTHDF1-dependent mechanism. These results indicate potential utility biomarker panel for prognostic prediction neuroblastoma.

Language: Английский

Emerging Roles of RNA Methylation in Development DOI
Mengke Wang, Chun‐Chun Gao, Yun‐Gui Yang

et al.

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(23), P. 3417 - 3427

Published: Nov. 15, 2023

More than 170 different types of chemical modifications have been identified on diverse RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) ubiquitous post-transcriptional modification are widely involved in regulating metabolic processes such RNA degradation, translation, stability, export, mediating important physiological pathological stress regulation, immune response, development, tumorigenesis. Recently, regulatory role during developmental is getting more attention. Therefore, development low-input even single-cell high-resolution sequencing technologies crucial for exploration roles these biological events trace samples.This account focuses various processes. We describe distribution characteristics modifications, catalytic enzymes, binding proteins, technologies. dynamically reversible, which can be catalyzed by methyltransferases eliminated demethylases. m6A most abundant eukaryote mRNA, mainly concentrated near stop codon, involves metabolism regulation. m5C, another studied modification, has a organisms species, enriched regions downstream translation initiation sites broadly distributes across whole coding sequence (CDS) mammalian mRNAs. m1A, with lower abundance m6A, distributed types, locates 5' untranslated region (5'UTR) mRNA regulates translation. m7G, one common eukaryotes, at cap internal positions RNAs recently gained considerable attention.Thanks to technology, found regulate tumorigenic process, including tumor proliferation, invasion, metastasis modulating oncogenes suppressor genes, affect oocyte maturation embryonic through maternal zygotic genes. m5C related proteins participate plant growth, neural stem cell differentiation dependent manner. m1A also revealed m7G dysregulation neurodevelopmental disorders neurodegenerative diseases.Collectively, we summarized gradually exhibited methylation discussed possibility candidate biomarkers potential therapeutic targets. The technological anticipated major driving force expand our knowledge this field.

Language: Английский

Citations

28
Ovarian aging: energy metabolism of oocytes DOI Creative Commons
Shenglan Bao, Tailang Yin,

Su Liu

et al.

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 31, 2024

Abstract In women who are getting older, the quantity and quality of their follicles or oocytes decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, lower oocytes. As more choose to delay childbirth, decline in fertility associated with age has become a significant concern for modern women. The oocyte key indicator aging. Many studies suggest that age-related changes energy metabolism may impact quality. Changes affect adenosine 5'-triphosphate (ATP) production, but how related products proteins influence remains largely unknown. review focuses on aging its potential quality, as well therapeutic strategies partially metabolism. research aims enhance our understanding metabolism, identification biomarkers treatment methods.

Language: Английский

Citations

14
FKBP5 regulates trophoblast-macrophage crosstalk in recurrent spontaneous abortion through PI3K/AKT and NF-κB signaling pathways DOI
Xin Chen, Qianlin Song,

Jia Yu Wang

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 209, P. 55 - 69

Published: Oct. 10, 2023

Language: Английский

Citations

13
Trimethylamine N-oxide aggravates human aortic valve interstitial cell inflammation by regulating the macrophages polarization through a N6-methyladenosine-mediated pathway DOI

Liming Wen,

Xiangjie Lin,

Dongtu Hu

et al.

Atherosclerosis, Journal Year: 2025, Volume and Issue: 402, P. 119109 - 119109

Published: Jan. 30, 2025

Language: Английский

Citations

0
Ultrafine Particulate Matter Exacerbates the Risk of Delayed Neural Differentiation: Modulation Role of METTL3-Mediated m6A Modification DOI
Rui Wang, Yutong Liu,

Lifan Fan

et al.

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Air pollution, especially from ultrafine particles (PM0.1, ≤0.1 μm), is increasingly recognized for its detrimental effects on health. The influence of PM0.1 neurodevelopmental disorders and underlying mechanisms remain incompletely understood but are significant concern. Through an investigation using mouse embryonic stem cells (mESCs), our study has uncovered disruptions in cell cycle dynamics, reduced neural precursor formation, impaired neurogenesis during mESC differentiation as a result PM0.1-induced toxicity. By employing N6-methyladenosine (m6A) methylated RNA immunoprecipitation sequencing bioinformatics, we identified Zic1 key target developmental disturbances. Our mechanistic findings indicate that enhances m6A methylation by upregulating Mettl3, leading to decreased mRNA stability expression this gene. Furthermore, the efficacy METTL3 inhibitor alleviating nerve impairments emphasizes significance pathway. In addition, source analysis, molecular docking, toxicity analyses show PAHs with higher ring structures combustion sources competitively bind METTL3, potentially exacerbating This not only underscores severe impact neurodevelopment also reveals pivotal role modification mediating these effects, providing valuable insights potential therapeutic targets mitigating PM0.1-related health risks.

Language: Английский

Citations

0
METTL3 suppressing SLC31A1 m6A modification regulates trophoblast migration and invasion DOI
Song Wang,

Yixiong Lin,

Qiong Deng

et al.

Placenta, Journal Year: 2025, Volume and Issue: 164, P. 21 - 30

Published: March 6, 2025

Language: Английский

Citations

0
Placental RTN3L‐dependent ER‐Phagy Contributes to Fetal Testicular Dysplasia Upon Environmental Stress DOI Creative Commons

Ye‐Xin Luo,

Hua Zhu, Binbin Huang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Abstract Prenatal environmental stress damages fetal testicular development, leading to male infertility. However, the precise mechanisms underlying impact of gestational on development require further investigation. This study demonstrates that stressor cadmium exposure caused placental estradiol synthesis inhibition and dysplasia. Gestational supplementation restores dysplasia by stress‐induced inhibition. Analysis human placentae cadmium‐stimulated primary trophoblasts confirmed ER‐phagy is associated with in placentae. Subsequently, data reveals significantly activates RTN3L‐mediated ER‐phagy. RTN3L ‐deficient cells Rtn3l ‐specific knockout mice confirm stress‐activated inhibited synthesis. Total N6‐methyladenosine level increasing stress‐exposed METTL3‐mediated modification suppression obviously restrains RTN3L‐dependent In conclusion, mRNA modification, inhibiting synthesis, contributing The early prevention treatment adult infertility from perspective fetal‐derived diseases.

Language: Английский

Citations

0
M6Allele: a toolkit for detection of allele-specific RNA N6-methyladenosine modifications DOI Creative Commons
Yin Zhang,

Lin Tang,

Shengyao Zhi

et al.

GigaScience, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 1, 2025

Abstract Background Allelic gene-specific regulatory events are crucial mechanisms in organisms, pivotal to many fundamental biological processes such as embryonic development and chromosome inactivation. gene imbalance manifests at both RNA expression epigenetic levels. Recent research has unveiled allelic-specific regulation of N6-methyladenosine (m6A), emphasizing the need for its precise identification. However, prevailing approaches primarily focus on screening allele-specific genetic variations associated with m6A, but not truly identify allelic m6A events. Therefore, construction a novel algorithm dedicated identifying (ASm6A) signals is still necessary comprehensively understanding mechanism ASm6A. Findings To address this limitation, we have developed meta-analysis approach using hierarchical Bayesian models accurately detect ASm6A peak level from MeRIP-seq data. For user convenience, introduce unified analysis pipeline named M6Allele, streamlining assessment significant across single paired samples. Applying M6Allele data pulmonary fibrosis lung adenocarcinoma reveals enrichment key genes these diseases, suggesting their potential involvement disease regulation. Conclusions Our effort provides method precisely level, elucidates interplay human health genetics, paves new visual angle research. The software freely available https://github.com/RenLabBioinformatics/M6Allele under MIT license.

Language: Английский

Citations

0
The Role of N6-methyladenosine Modification in Gametogenesis and Embryogenesis: Impact on Fertility DOI Creative Commons
Yujie Wang, Chen Yang, H. Sun

et al.

Genomics Proteomics & Bioinformatics, Journal Year: 2024, Volume and Issue: 22(4)

Published: June 27, 2024

The most common epigenetic modification of messenger RNAs (mRNAs) is N6-methyladenosine (m6A), which mainly located near the 3' untranslated region mRNAs, stop codons, and within internal exons. biological effect m6A dynamically modulated by methyltransferases (writers), demethylases (erasers), m6A-binding proteins (readers). By controlling post-transcriptional gene expression, has a significant impact on numerous functions, including RNA transcription, translation, splicing, transport, degradation. Hence, influences various physiological pathological processes, such as spermatogenesis, oogenesis, embryogenesis, placental function, human reproductive system diseases. During gametogenesis genetic material undergoes changes, epigenomic modifications m6A. From spermatogenesis oogenesis to formation an oosperm early changes occur at every step. abnormalities can lead gamete abnormalities, developmental delays, impaired fertilization, maternal-to-zygotic transition blockage. Both mice humans with abnormal exhibit fertility. In this review, we discuss dynamic effects its regulators embryonic development review possible mechanisms infertility caused changes. We also drugs currently used manipulate provide prospects for prevention treatment level.

Language: Английский

Citations

3
METTL14 promotes neuroblastoma formation by inhibiting YWHAH via an m6A-YTHDF1-dependent mechanism DOI Creative Commons
Jianwei Wang, Hongli Yin, Gen Li

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 22, 2024

Abstract Neuroblastoma (NB) is a common childhood tumor with high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact methyltransferase-like 14 (METTL14) on progression been extensively studied various types cancer. However, specific influence METTL14 NB remains unexplored. Using data from Target database, our study revealed upregulation high-risk patients, strong correlation poor prognosis. Furthermore, we identified ETS1 YY1 as upstream regulators that control METTL14. In vitro experiments involving knockdown cells demonstrated inhibition cell proliferation, migration, invasion. addition, suppressing inhibited tumorigenesis nude mouse models. Through MeRIP-seq RNA-seq analyses, further discovered YWHAH downstream target Mechanistically, observed methylated transcripts, particularly those 5′ UTR, were specifically recognized by m6A “reader” protein YTHDF1, leading to degradation mRNA. Moreover, downregulation activated PI3K/AKT signaling pathway, promoting activity. Overall, provides valuable insights into oncogenic effects cells, highlighting its inhibiting through an m6A-YTHDF1-dependent mechanism. These findings also suggest potential utility biomarker panel for prognostic prediction patients.

Language: Английский

Citations

2