Roles and therapeutic implications of m6A modification in cancer immunotherapy

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

Published: March 7, 2023

Recent studies have demonstrated that N6-methyladenosine (m6A), the most abundant, dynamic, and reversible epigenetic RNA modification in eukaryotes, is regulated by a series of enzymes, including methyltransferases (writers), demethylases (erasers), m6A recognition proteins (readers). Aberrant regulation pivotal for tumorigenesis, progression, invasion, metastasis, apoptosis malignant tumors. Immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, as recognized 2018 Nobel Prize Medicine Physiology. However, not all patients response to ICI therapy, which thought be result intricate immune escape mechanisms. Recently, numerous suggested novel role tumor evasion. Herein, we review relevant mechanisms regulators regulating various key signaling pathways biology how modifications regulate expression checkpoints, opening new window understand roles In addition, highlight prospects development directions future combined immunotherapy strategies based on targeting, providing promoting treatment outcomes inhibitors.

Language: Английский

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YTHDF2 promotes multiple myeloma cell proliferation via STAT5A/MAP2K2/p-ERK axis

Oncogene, Journal Year: 2022, Volume and Issue: 41(10), P. 1482 - 1491

Published: Jan. 24, 2022

Language: Английский

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N6-methyladenosine RNA modification in PD-1/PD-L1: Novel implications for immunotherapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(3), P. 188873 - 188873

Published: Feb. 25, 2023

Language: Английский

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The regulation and potential roles of m6A modifications in early embryonic development and immune tolerance at the maternal-fetal interface

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 26, 2022

The immune microenvironment at the maternal-fetal interface was determined by crosstalk between trophoblast and maternal-derived cells, which dynamically changed during whole gestation. Trophoblasts act as innate cells dialogue with to ensure early embryonic development, depending on local microenvironment. Therefore, dysfunctions in trophoblasts maternal decidual contribute pregnancy complications, especially recurrent loss pregnancy. Since many unknown regulatory factors still affect complex status, exploring new potential aspects that could influence is essential. RNA methylation plays an important role contributing transcriptional regulation of various cells. Sufficient studies have shown crucial roles N6-methyladenosine (m6A)- m6A-associated- regulators embryogenesis implantation. They are also essential regulating adaptive response shaping systemic However, function m6A modifications lacks wide research. This review highlights critical functions summarizes reported research tumor microenvironment, identifies value trophoblasts, interface. more likely embryogenesis, placentation shape Uncovering these mechanisms provide novel therapeutic targets for

Language: Английский

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M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 26, 2024

N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role of tumor microenvironment (TME) cell infiltration several tumors. Nevertheless, potential and mechanism nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data clinical information from GSE102349, GSE53819 datasets obtained Gene Expression Omnibus (GEO) was used for differential gene subsequent analysis. Consensus clustering to identify m6A-related molecular patterns 88 NPC samples based on prognostic regulators using Univariate Cox The TME cell-infiltrating characteristics each subclass were explored single-sample set enrichment (ssGSEA) algorithm CIBERSORT algotithm. DEGs between two subclasses screened edgeR package. signature predicated nomogram constructed DEGs. determined immunohistochemistry (IHC) Chi-square test analysis significance difference categorical variables. And survival performed Kaplan–Meier plots log-rank tests. divided into subclasses. analyses indicated cluster 1 characterized by immune-related metabolism pathways activation, better response anit-PD1 anti-CTLA4 treatment chemotherapy. 2 stromal low HLA family immune checkpoints, worse anti-PD1 Furthermore, we identified 1558 signatures predicate progression-free (PFS) patients. Compared non-tumor samples, REEP2, TMSB15A, DSEL, ID4 upregulated samples. High REEP2 TMSB15A showed poor interaction ID4, detected. Our finding plays an important heterogeneity complexity.

Language: Английский

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Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 11, 2022

N6-methyladenosine (m6A) is a dynamic, reversible post-transcriptional modification, and the most common internal modification of eukaryotic messenger RNA (mRNA). Considerable evidence now shows that m6A alters gene expression, thereby regulating cell self-renewal, differentiation, invasion, apoptotic processes. M6A methylation disorders are directly related to abnormal metabolism, which may lead tumor formation. methyltransferase dominant catalyst during modification; it removes demethylase, promotes recognition by binding proteins, regulates mRNA metabolic Bladder cancer (BC) urinary system malignant tumor, with complex etiology high incidence rates. A well-differentiated or moderately differentiated pathological type at initial diagnosis accounts for patients BC. For superficial bladder urothelial carcinoma, prognosis normally good after surgery. However, due poor epithelial BC proliferation infiltration invasive metastatic BC, lowers 5-years survival rate significantly affects clinical treatments in elderly patients. Here, we review latest progress research investigate its regulation on occurrence development.

Language: Английский

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Identification of fatty acid anabolism patterns to predict prognosis and immunotherapy response in gastric cancer

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 4, 2025

Gastric cancer (GC), one of the most common and heterogeneous malignancies, is second leading cause death worldwide closely related to dietary habits. Fatty acid main nutrients human beings, which diabetes, hypertension other diseases. However, correlation between fatty metabolism development progression GC remains largely unknown. Here, we profiled genetic alterations anabolism-related genes (FARGs) in gastric samples from TCGA cohort GEO database evaluate possible relationships their internal regulatory mechanism. Through consistent clustering functional enrichment analysis, three distinct anabolism clusters gene subtypes were identified participate different biological pathways, correlated with characteristics immune cell infiltration clinical prognosis. Importantly, a distinctive FA-score was constructed through principal component analysis quantify each patient. Further showed patients grouped high group characterized greater tumor mutational burden (TMB) higher microsatellite stability (MSI-H), may be more aeschynomenous immunotherapy had favorable Altogether, our bioinformatics based on FARGs uncovered potential roles GC, provide newly prognostic information novel approaches for promoting individualized GC.

Language: Английский

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Zhishi Daozhi decoction alleviates constipation induced by a high-fat and high-protein diet via regulating intestinal mucosal microbiota and oxidative stress

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

Published: Sept. 18, 2023

Background A growing body of evidence has demonstrated that a high-fat and high-protein diet (HFHPD) causes constipation. This study focuses on understanding how the use Zhishi Daozhi decoction (ZDD) affects intricate balance intestinal microorganisms. The insights gained from this investigation hold potential to offer practical clinical approaches mitigate constipation-related issues associated with HFHPD. Materials methods Mice were randomly divided into five groups: normal (MN) group, natural recovery (MR) low-dose ZDD (MLD) medium-dose (MMD) high-dose (MHD) group. After constipation model was established by HFHPD combined loperamide hydrochloride (LOP), different doses used for intervention. Subsequently, contents cholecystokinin (CCK) calcitonin gene-related peptide (CGRP) in serum, superoxide dismutase (SOD), malondialdehyde (MDA) liver determined. DNA mucosa extracted, 16S rRNA amplicon sequencing analyze changes mucosal microbiota. Results treatment, CCK content MR group decreased CGRP increased, but not significant. In addition, SOD significantly lower than MLD, MMD, MHD groups, MDA higher MN, groups. Constipation modeling intervention changed structure induced HFHPD, relative abundance pathogenic bacteria such as Aerococcus, Staphylococcus, Corynebacterium, Desulfovibrio, Clostridium , Prevotella increased. ZDD, these decreased, Candidatus Arthromitus Tropane, piperidine, pyridine alkaloid biosynthesis pathways increased Conclusion can increase mucosa, while effectively relieve constipation, reduce bacteria, alleviate oxidative stress injury. beneficial which is more conducive treatment

Language: Английский

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Distinct immune and inflammatory response patterns contribute to the identification of poor prognosis and advanced clinical characters in bladder cancer patients

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 27, 2022

Due to the molecular heterogeneity, most bladder cancer (BLCA) patients show no pathological responses immunotherapy and chemotherapy yet suffer from their toxicity. This study identified validated three distinct stable clusters of BLCA in cross-platform databases based on personalized immune inflammatory characteristics. H&E-stained histopathology images confirmed infiltration cells among clusters. Cluster-A was characterized by a favorable prognosis low but showed highest abundance prognosis-related cell activity. Cluster-B featured worst high infiltration, numerous unfavorable exist. Cluster-C had infiltration. Based machine learning, highly precise predictive model (immune signature, IIRS), including FN1, IL10, MYC, CD247, TLR2, developed identify IIRS-score group that poor advanced clinical Compared other published models, IIRS AUC 5 years overall survival (OS) value predicting 1- 3- year OS. Moreover, an excellent performance chemotherapy's response. According immunohistochemistry qRT-PCR, genes were differentially expressed between tumor tissues with corresponding normal or adjacent tissues. Finally, immunohistochemical analyses performed 13 further demonstrate score is valid substitute for IIR patterns can contribute identifying In conclusion, we established novel depicting pattern could independently predict OS acts as biomarker characters chemotherapy.

Language: Английский

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Inflammation-related research within the field of bladder cancer: a bibliometric analysis

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

Published: June 7, 2023

In recent years, the link between inflammation and bladder cancer(BC) has received much attention. However, there were no relevant bibliometric studies to analyze inflammation-related research within this field of BC.

Language: Английский

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