METTL14‑mediated RNA methylation in digestive system tumors

International Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 52(3)

Published: Aug. 4, 2023

N6‑methyladenosine (m6A) RNA methylation is one of the most common post‑transcriptional modification mechanism in eukaryotes. m6A involved almost all stages mRNA life cycle, specifically regulating its stability, splicing, export and translation. Methyltransferase‑like 14 (METTL14) a particularly important 'writer' that can recognize substrates. METTL14 has been documented to improve activity catalytic efficiency METTL3. However, as individual proteins they also regulate different biological processes. Malignancies digestive system are some malignancies found humans, which typically associated with poor prognoses limited clinical solutions. METTL14‑mediated implicated both potentiation inhibition tumor growth, cell invasion metastasis, addition drug resistance. In present review, research progress regulatory mechanisms were summarized. addition, future directions potential for application examined.

Language: Английский

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Exploring the prognostic potential of m6A methylation regulators in low-grade glioma: implications for tumor microenvironment modulation

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Jan. 3, 2024

The biological behavior of low-grade glioma (LGG) is significantly affected by N6-methyladenosine (m6A) methylation, an essential epigenetic alteration. Therefore, it crucial to create a prognostic model for LGG utilizing genes that regulate m6A methylation. Using TCGA and GTEx databases. We examined modulator levels in normal tissues, investigated PD-L1 PD-1 expression, immune scores, cell infiltration, tumor microenvironment (TIME) potential underlying mechanisms different clusters. also performed immunohistochemistry RT-qPCR identify adjustment factor. results showed regulatory element expression was increased tissues associated with TMIE. A substantial increase high-risk cohorts observed. positively correlated FTO, ZCCHC4, HNRNPD, whereas negatively ZC3H7B, HNRNPD. signature created using regulators RNA methylation shown be strongly the overall survival patients, FTO ZCCHC4 were confirmed as independent markers clinical samples. Furthermore, revealed TIME characteristics between two groups indicating disrupted signaling pathways LGG. Our present play vital role regulating PD-L1/PD-1 infiltration cells, thereby exerting sizable impact on have precise predictive value prognosis

Language: Английский

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RNA modifications in cancer immune therapy: regulators of immune cells and immune checkpoints

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

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Demethylase FTO enhances the PI3K/Akt signaling to promote gastric cancer malignancy

Medical Oncology, Journal Year: 2023, Volume and Issue: 40(5)

Published: March 27, 2023

Language: Английский

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Glutamine metabolism genes prognostic signature for stomach adenocarcinoma and immune infiltration: potential biomarkers for predicting overall survival

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: June 12, 2023

Stomach adenocarcinoma (STAD), caused by mutations in stomach cells, is characterized poor overall survival. Chemotherapy commonly administered for cancer patients following surgical resection. An imbalance tumor metabolic pathways connected to genesis and growth. It has been discovered that glutamine (Gln) metabolism plays a crucial role cancer. Metabolic reprogramming associated with clinical prognosis various cancers. However, the of genes (GlnMgs) fight against STAD remains poorly understood.GlnMgs were determined samples from TCGA GEO datasets. The databases provide information on stemness indices (mRNAsi), gene mutations, copy number variations (CNV), mutation burden (TMB), characteristics. Lasso regression was performed build prediction model. relationship between expression Gln investigated using co-expression analysis.GlnMgs, found be overexpressed high-risk group even absence any symptomatology, demonstrated strong predictive potential outcomes. GSEA highlighted immunological tumor-related group. Immune function m6a differed significantly low- groups. AFP, CST6, CGB5, ELANE may linked oncology process patients. prognostic model, CNVs, single nucleotide polymorphism (SNP), medication sensitivity all revealed link gene.GlnMgs are development STAD. These corresponding models aid predicting GlnMgs immune cell infiltration microenvironment (TME) possible therapeutic targets Furthermore, signature presents credible alternative outcomes, suggesting these could open new field study STAD-focused therapy Additional trials needed validate results current study.

Language: Английский

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Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis

The International Journal of Biological Markers, Journal Year: 2023, Volume and Issue: 38(3-4), P. 185 - 193

Published: July 2, 2023

Background N6-methyladenosine (m 6 A) methylation is known as the research hotspot for tumor epimodification, and its associated methyltransferase-like3 (METTL3) significantly differentially expressed in gastric carcinoma, but clinical value has not been summarized. This meta-analysis aimed to evaluate prognostic significance of METTL3 carcinoma. Material methods Databases, including PubMed, EMBASE (Ovid platform), Science Direct, Scopus, MEDLINE, Google Scholar, Web Science, Cochrane Library, were used identify relevant eligible studies. The endpoints included overall survival, progression-free recurrence-free post-progression disease-free survival. Hazard ratios (HR) with 95% confidence intervals (CI) correlate expression prognosis. Subgroup sensitivity analyses performed. Results Seven studies involving 3034 carcinoma patients recruited this meta-analysis. analysis showed that high was poorer survival (HR = 2.37, CI 1.66–3.39, P < 0.01) unfavorable 2.58, 1.97–3.38, 0.01), did 1.48, 1.19–1.84, 0.01)/recurrence-free 2.62, 1.93–5.62, 0.01)/post-progression 1.53, 1.22–1.91, 0.01). found worse Chinese 2.21, 1.48–3.29, sample source from formalin-fixed, paraffin-embedded tissues 2.66, 1.79–3.94, reported directly articles group 2.42, 1.66–3.53, subgroup performed based on size, detected method, follow-up same results. Conclusions High predicts poor prognosis indicating promise a biomarker. Systematic review registration: https://www.crd.york.ac.uk/prospero , ID CRD42023408519

Language: Английский

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Pyrimidine metabolism regulator-mediated molecular subtypes display tumor microenvironmental hallmarks and assist precision treatment in bladder cancer

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Aug. 17, 2023

Background Bladder cancer (BLCA) is a common urinary system malignancy with significant morbidity and death rate worldwide. Non-muscle invasive BLCA accounts for over 75% of all cases. The imbalance tumor metabolic pathways associated formation proliferation. Pyrimidine metabolism (PyM) complex enzyme network that incorporates nucleoside salvage, de novo nucleotide synthesis, catalytic pyrimidine degradation. Metabolic reprogramming linked to clinical prognosis in several types cancer. However, the role Genes (PyMGs) BLCA-fighting process remains poorly understood. Methods Predictive PyMGs were quantified samples from TCGA GEO datasets. provided information on stemness indices (mRNAsi), gene mutations, CNV, TMB, corresponding features. prediction model was built using Lasso regression. Co-expression analysis conducted investigate relationship between expression PyM. Results overexpressed high-risk sample absence other symptoms, demonstrating their predictive potential outcome. Immunological tumor-related identified group by GSWA. Immune function m6a varied significantly risk groups. In patients, DSG1, C6orf15, SOST, SPRR2A, SERPINB7, MYBPH, KRT1 may participate oncology process. differed two prognostic model, CNVs, single polymorphism (SNP), drug sensitivity showed connections. Conclusions BLCA-associated are available provide guidance immunological setting give evidence formulation PyM-related molecularly targeted treatments. interactions immune cells serve as therapeutic targets.

Language: Английский

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m6A methylation modification and immune cell infiltration: implications for targeting the catalytic subunit m6A-METTL complex in gastrointestinal cancer immunotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 15, 2023

N 6 -methyladenosine (m A) methylation modification is a ubiquitous RNA involved in the regulation of various cellular processes, including stability, metabolism, splicing and translation. Gastrointestinal (GI) cancers are some world’s most common fatal cancers. Emerging evidence has shown that m A dynamically regulated by complex network enzymes catalytic subunit A-METTL (MAC)-METTL3/14, core component methyltransferases, participates development progression GI Furthermore, it been METTL3/14 modulates immune cell infiltration an A-dependent manner TIME (Tumor microenvironment), thereby altering response cancer cells to ICIs (Immune checkpoint inhibitors). Immunotherapy emerged as promising approach for treating Moreover, targeting expression its downstream genes may improve patient immunotherapy. Therefore, understanding role MAC pathogenesis impact on provide new insights into effective therapeutic strategies

Language: Английский

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METTL3 as a potential therapeutic target in gastric cancer

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Nov. 29, 2024

Gastric cancer (GC) is one of the leading causes cancer-related death worldwide. N6-methyladenosine (m6A) modification most prominent epigenetic eukaryotic mRNAs, and methyltransferase-like 3 (METTL3), a core component methyltransferase complex, catalyzes m6A modification. The results previous studies indicate that expression level METTL3 significantly elevated in gastric tissues cells. In addition, fluctuations levels induced by are closely associated with malignant progression tumors as well poor prognosis patients cancer. this review, we focus on potential mechanism cancer, through our analysis, suggest targeting could be new therapeutic tool for treating GC.

Language: Английский

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Characterization of growth arrest-specific transcript 5 and growth arrest-specific transcript 5-related m6A gene signature in glioma: An observational study

Medicine, Journal Year: 2024, Volume and Issue: 103(39), P. e39414 - e39414

Published: Sept. 27, 2024

Glioma remains a significant clinical challenge and poses dismal patient prognosis. This study focused on the long noncoding ribonucleic acid growth arrest-specific transcript 5 (GAS5) explored role of GAS5 GAS5-related m6A genes in glioma. We mechanisms expression glioma using bioinformatic analysis based data from Cancer Genome Atlas, GSE1142, Chinese Atlas databases. Kaplan–Meier curve analysis, nomogram construction, immune cell infiltration, drug sensitivity, mutations, pathway analyses were performed to determine mechanism Spearman correlation weighted gene co-expression used identify gene. Furthermore, we between GAS5, gene, traits variance. The suggested that patients with high expressions had better survival. constructed indicated was an independent prognostic factor. significantly correlated plasma cells. associated biological processes, including oxidative phosphorylation, proteasome, ribosome mitotic spindle. sensitivity erlotinib gemcitabine. Differentially expressed histology ( P = 2.8e−09), grade 3.7e−05), isocitrate dehydrogenase (IDH) mutation 3.4e−17), 1p/19q co-deletion (Codel) status 1.7e−08), IDH Codel 2.9e−18). Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) .008) 2.1e−05). HNRNPC reflected malignant are abnormal could be important biomarker for guiding gemcitabine use treatment. heterogeneous potential diagnostic markers

Language: Английский

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