The role of RNA methylation in tumor immunity and its potential in immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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RNA modifications in cancer

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such N6‐methyladenosine (m 6 A) 5‐methylcytosine 5 C), implicated in various cellular processes. These regulated by proteins write, erase, read modulate stability, splicing, translation, degradation. Recent studies have highlighted their roles metabolic reprogramming, signaling pathways, cell cycle control, which essential for tumor proliferation survival. Despite these scientific advances, the precise mechanisms affect remain inadequately understood. This review comprehensively examines role play proliferation, metastasis, programmed death, including apoptosis, autophagy, ferroptosis. It explores effects on epithelial–mesenchymal transition (EMT) immune microenvironment, particularly metastasis. Furthermore, modifications’ potential therapies, conventional treatments, immunotherapy, targeted is discussed. By addressing aspects, this aims to bridge current research gaps underscore therapeutic of targeting improve treatment strategies patient outcomes.

Language: Английский

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Characterization of the m6A/m1A/m5C/m7G‐related regulators on the prognosis and immune microenvironment of glioma by integrated analysis of scRNA‐seq and bulk RNA‐seq data

The Journal of Gene Medicine, Journal Year: 2024, Volume and Issue: 26(2)

Published: Feb. 1, 2024

Proliferation, metabolism, tumor occurrence and development in gliomas are greatly influenced by RNA modifications. However, no research has integrated the four methylation regulators of m6A, m1A, m5C m7G to analyze their relationship with glioma prognosis intratumoral heterogeneity. Based on three in-house single-cell RNA-sequencing (scRNA-seq) data, heterogeneity characteristics m6A/m1A/m5C/m7G-related were elucidated. publicly available bulk (RNA-seq) a risk-score system for predicting overall survival (OS) was established machine learning methods multivariate Cox regression analysis, validated an independent cohort. Seven cell types identified scRNA-seq 22 among marker genes different subtypes discovered. Three selected construct prognostic model, including EIFA, NSUN6 TET1. The high-risk patients showed higher immune checkpoint expression, microenvironment scores, as well mutation burden poorer compared low-risk patients. Additionally, area under curve values risk score nomogram 0.833 0.922 3 year 0.759 0.885 5 gliomas. EIF3A significantly highly expressed tissues our data (p < 0.05). These findings may contribute further understanding role gliomas, provide novel reliable biomarkers treatment.

Language: Английский

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RNA methylation: A new promising biomaker in cancer liquid biopsy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189337 - 189337

Published: April 1, 2025

Language: Английский

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Pan-cancer analysis of the prognosis and immune infiltration of NSUN7 and its potential function in renal clear cell carcinoma

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

Published: March 18, 2025

NSUN7, an enzyme responsible for the RNA m5c modification, has been recognized as a valuable indicator predicting and diagnosing array of cancer. Nevertheless, there is still scarcity thorough analyses exploring its diagnostic, predictive, immune system-related importance in various types We integrated multiple publicly available databases, including TCGA, TISIDB, TISCH2, UALCAN, to comprehensively investigate role NSUN7 pan-cancer across omics data types. The research included examining survival rates, genetic mutations, cell presence tumors, analyzing differences gene expression, studying individual cells, among other things. expression showed increase 12 cancer decrease another was discovered be linked with enhanced rates bladder urothelial carcinoma (BLCA), kidney renal clear (KIRC), papillary (KIRP), lung adenocarcinoma (LUAD), pheochromocytoma paraganglioma (PCPG), skin cutaneous melanoma (SKCM), uveal (UVM).On hand, seemed have detrimental impact on prognosis glioblastoma multiforme/brain lower grade glioma (GBMLGG), adrenocortical (ACC),acute myeloid leukemia (LAML), stomach (STAD), brain (LGG). Furthermore, our experimental validation confirmed inhibitory effect proliferation while elucidating specific part blocking cycle progression. findings underscore potential utility prognostic patients offer insights into mechanisms underlying initiation

Language: Английский

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Inhibition of NSUN3 suppresses immune escape in non-small cell lung cancer through stabilizing PD-L1 in a 5-methyladenosine dependent way

Clinics, Journal Year: 2025, Volume and Issue: 80, P. 100662 - 100662

Published: Jan. 1, 2025

Alterations in 5-methyladenosine (m5C) RNA methyltransferase have been implicated the pathogenesis of lung cancer. However, role NSUN3, a key m5C regulator, modulating PD-L1 expression and immune evasion Non-Small Cell Lung Cancer (NSCLC) remains poorly understood. NSUN3 levels NSCLC tissues cell lines were quantified using quantitative Reverse Transcription PCR (RT-qPCR). The impact modulation on cancer viability proliferation was assessed through CCK-8 assays colony formation experiments. To evaluate interactions, CD8+ T-cells co-cultured with cells, cytotoxic activity measured by an LDH cytotoxicity detection kit. vivo tumorigenic investigated subcutaneous tumor xenograft models. Mechanistic insights into NSUN3-PD-L1 interactions obtained m5C-RIP, RIP, dual-luciferase reporter assays. Elevated mRNA observed compared to normal controls. Functional studies demonstrated that knockdown significantly inhibited both A549 PC9 lines. Furthermore, depletion enhanced T-cell-mediated against cells suppressed growth vivo. Mechanistically, inhibition found stabilize mRNA, suggesting regulatory checkpoint modulation. present findings establish as oncogenic driver pathogenesis, functioning stabilization. identification this axis provides new molecular mechanisms underlying escape offers promising directions for developing targeted immunotherapies.

Language: Английский

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RNA m5C modification: from physiology to pathology and its biological significance

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

Published: April 30, 2025

RNA 5-methylcytosine (m5C) modification is a crucial epitranscriptomic mark that regulates stability, processing, and translation. Emerging evidence highlights its essential role in various physiological processes, including cellular differentiation, stem cell maintenance, immune responses. Dysregulation of m5C has been implicated multiple pathological conditions, particularly cancer, neurodegenerative disorders, metabolic diseases. This review provides comprehensive overview the molecular mechanisms governing deposition, functional consequences normal physiology, contributions to disease pathogenesis. Furthermore, we discuss potential as biomarker therapeutic target, offering new insights into biological significance clinical relevance.

Language: Английский

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ALKBH5 promotes the development of lung adenocarcinoma by regulating the polarization of M2 macrophages through CDCA4

Gene, Journal Year: 2023, Volume and Issue: 895, P. 147975 - 147975

Published: Nov. 8, 2023

Language: Английский

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RNA M6A modification shaping cutaneous melanoma tumor microenvironment and predicting immunotherapy response

Pigment Cell & Melanoma Research, Journal Year: 2024, Volume and Issue: 37(4), P. 496 - 509

Published: April 16, 2024

Abstract Recent years have seen rising mortality rates linked to cutaneous melanoma (SKCM), despite advances in immunotherapy. Understanding RNA N6‐methyladenosine (M6A) significance SKCM is crucial for prognosis, tumor microenvironment (TME), immune cell presence, and immunotherapy efficacy. We analyzed 23 M6A regulators using samples from TCGA GEO databases, identifying three modification patterns TME infiltration. Principal component analysis (PCA) yielded an score individual tumors, utilizing patient gene expression profiles CNV data TCGA. play a role development progression, influencing attributes such as inflammatory stage, subtype, interstitial activity, genetic mutations. The independently predicts outcomes correlates with improved response immunotherapy, validated across anti‐PD‐1 anti‐PD‐L1 therapy cohorts. modifications significantly impact the landscape, serving predictive marker response. Integrating M6A‐related information into clinical practice could revolutionize management treatment strategies.

Language: Английский

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Prognostic value of lung immune prognostic index in non-small cell lung cancer patients receiving immune checkpoint inhibitors: a meta-analysis

Pathology & Oncology Research, Journal Year: 2024, Volume and Issue: 30

Published: June 20, 2024

Until now, it has been difficult to accurately predict the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). A novel indicator, immune prognostic index (LIPI), shown relatively high value solid cancer. Therefore, this study aimed further identify association between LIPI and survival NSCLC who receive checkpoint inhibitors (ICIs).

Language: Английский

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