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

---

METTL3-Mediated N6-Methyladenosine mRNA Modification and cGAS-STING Pathway Activity in Kidney Fibrosis

Journal of the American Society of Nephrology, Journal Year: 2024, Volume and Issue: 35(10), P. 1312 - 1329

Published: June 10, 2024

Chemical modifications on RNA profoundly affect function and regulation. m6A, the most abundant modification in eukaryotes, plays a pivotal role diverse cellular processes disease mechanisms. However, its importance is understudied human CKD samples regarding influence pathological

Language: Английский

---

METTL3-mediated NDUFB5 m6A modification promotes cell migration and mitochondrial respiration to promote the wound healing of diabetic foot ulcer

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 9, 2024

Abstract Background Diabetic foot ulcer (DFU) is the most devastating complication of diabetes mellitus (DM) and plays a major role in disability death DM patients. NADH: ubiquinone oxidoreductase subunit B5 (NDUFB5) an important maintaining mitochondrial respiration, but whether it involved regulating progression advanced glycation end products (AGEs)-mediated DFU still unclear. Methods Firstly, AGEs on cell viability, migration, respiration human umbilical vein endothelial cells (HUVECs) was explored vitro. Next, NDUFB5 expression detected samples AGEs-treated HUVECs, NDUFB5’s effect AGEs-induced HUVECs injury skin wound diabetic mice further clarified. In addition, m6A modification mediated by methyltransferase-like 3 (METTL3) investigated. Results promoted whereas fusion promoter M1 facilitated oxiadative knockdown HUVECs. Meanwhile, promotes healing mice. Besides, METTL3-mediated insulin like growth factor 2 mRNA binding protein (IGF2BP2) enhanced Furthermore, METTL3 increasing NDUFB5. Conclusion inhibits might serve as potential targets for therapy future.

Language: Английский

---

Specific deletion of Mettl3 in IECs triggers the development of spontaneous colitis and dysbiosis of T lymphocytes in mice

Clinical & Experimental Immunology, Journal Year: 2024, Volume and Issue: 217(1), P. 57 - 77

Published: March 20, 2024

Abstract The enzymatic core component of m6A writer complex, Mettl3, plays a crucial role in facilitating the development and progress gastric colorectal cancer (CRC). However, its underlying mechanism regulating intestinal inflammation remains unclear poorly investigated. First, characteristics Mettl3 expression inflammatory bowel diseases (IBD) patients were examined. Afterward, we generated mice line with epithelial cells (IECs)-specific deletion verified by various experiments. We continuously recorded compared physiological status including survival rate etc. between two groups. Subsequently, took advantage staining assays to analyze mucosal damage immune infiltration Mettl3WT Mettl3KO primary IECs. Bulk RNA sequencing was used pursuit differential genes (DEGs) associated signaling pathways after losing Mettl3. Pyroptosis-related proteins determine whether cell death caused pyroptosis. Eventually, CyTOF performed probe difference CD45+ cells, especially CD3e+ T-cell clusters In IBD patients, highly expressed inner-nucleus IECs while significantly decreased upon acute inflammation. IECs-specific KO triggered wasting phenotype developed spontaneous colitis. rate, body weight, length observed from 2 8 weeks lower than mice. degree even more serious their WT littermate. demonstrated that DEGs dramatically enriched NOD-signaling due loss colonic epithelium prone pyroptosis revealed T have altered Mettl3KO. Furthermore, there abnormal proliferation CD4+ markedly exhaustion CD8 + severe is located declined when occurs. prevented developing

Language: Английский

---

Cellular senescence: from homeostasis to pathological implications and therapeutic strategies

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

Published: Feb. 3, 2025

Cellular aging is a multifactorial and intricately regulated physiological process with profound implications. The interaction between cellular senescence cancer complex multifaceted, can both promote inhibit tumor progression through various mechanisms. M6A methylation modification regulates the of cells tissues by modulating senescence-related genes. In this review, we comprehensively discuss characteristics senescence, signaling pathways regulating biomarkers mechanisms anti-senescence drugs. Notably, review also delves into interactions cancer, emphasizing dual role senescent microenvironment in initiation, progression, treatment. Finally, thoroughly explore function mechanism m6A revealing its critical gene expression maintaining homeostasis. conclusion, provides comprehensive perspective on molecular biological significance offers new insights for development strategies.

Language: Английский

---

METTL3-modified exosomes from adipose-derived stem cells enhance the proliferation and migration of dermal fibroblasts by mediating m6A modification of CCNB1 mRNA

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: Feb. 15, 2025

Language: Английский

---

RNA Modification in Metabolism

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

ABSTRACT Epigenetic regulation in disease development has been witnessed within this decade. RNA methylation is the predominant form of epigenetic regulation, and most prevalent modification N6‐methyladenosine (m 6 A). Recently, emerged as a potential target for treatment. posttranscriptional gene expression that involved both physiological pathological processes. Evidence suggests m A significantly affects metabolism, its abnormal changes have observed variety diseases. Metabolic diseases are series caused by metabolic processes body, common include diabetes mellitus, obesity, nonalcoholic fatty liver disease, etc.; although pathogenesis these differs from each other to current understanding, recent studies suggested pivotal role modulating diseases, A‐based drug on agenda. This paper reviewed understanding hoping provide systematic information those area.

Language: Английский

---

Insights From m6A RNA Methylation: Biomarkers for Diagnosis of Acute Myocardial Infarction

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3589 - 3605

Published: March 1, 2025

Purpose: Acute myocardial infarction (AMI) is a major contributor to death. The purpose of this study explore circulating biomarkers for AMI diagnosis from the perspectives immunological microenvironment and N6-methyladenosine (m6A) RNA methylation regulation. Patients Methods: GSE59867 dataset was used download platform probe data conducting differential analysis m6A regulators. A diagnostic nomogram created utilizing random-forest method evaluated predictive power. m6A-related gene patterns were identified, their immune characteristics analyzed. Peripheral blood samples obtained validation in patient-based investigations using RT-qPCR. association between regulators clinical parameters examined via Spearman correlation analysis. Results: With model developed key regulators, two distinct subtypes showing significant variations infiltrating immunocyte abundance. In confirmation prediction, examination patient identified METTL3, WTAP, RBM15, ALKBH5, FTO, FMR1 as novel diagnosis. METTL3 FTO promising given that they showed positive with left ventricular ejection fraction. Conclusion: six suggested potential role m6A-mediated cell infiltration pathogenesis AMI. Keywords: acute infarction, infiltration, N6-methyladenosine, diagnosis, biomarker

Language: Английский

---

Chirality Regulates Macrophage Polarization for Tissue Regeneration Through Bidirectionally Modulating WTAP‐Mediated m⁶A Modification

Small Structures, Journal Year: 2024, Volume and Issue: 5(5)

Published: Feb. 2, 2024

Chirality, a fundamental design feature at all levels of life organization, has shown great capability in guiding cell‐fate determination and tissue regeneration. Chirality‐directed differentiation programs involve remarkable changes transcriptional networks, yet whether epigenetic regulatory events are also required is less well understood. Herein, by combining high‐throughput m 6 A MeRIP sequencing, RIP‐qPCR, gene modulation techniques, it demonstrated that biomimetic chiral nanofibrils can bidirectionally regulate wilms tumor 1 associated protein (WTAP)‐mediated RNA methylation to guide macrophages polarization for The biomimic nanofibril hydrogels fabricated using self‐assembly approach based on C2‐symmetric phenylalanine derivatives. In vitro vivo studies indicated the L‐nanofibrils exhibit greater propensity promote M2‐macrophage than D‐nanofibrils, thereby favoring osteogenesis. Then, A‐MeRIP sequencing revealed unique chirality‐dependent level macrophages, which was gated competitive pair CCM3‐FAK through enantioselectively integrin recognition. considerably suppressed WTAP‐mediated promoting Itgα3‐FAK expression paxillin‐driven mechanotransduction, whereas D‐nanofibrils induced ItgαV‐CCM3 suppressing mechanotransduction. Furthermore, gain‐of‐function loss‐of‐function experiments RIP‐qPCR demonstrate WTAP could direct macrophage via manipulating functional molecule B7‐H3 (CD276). Thus, mechano‐epigenetic mechanism chirality‐mediated unveiled, holds promise realm assisted regenerative material design.

Language: Английский

---

Elevated WTAP promotes hyperinflammation by increasing m6A modification in inflammatory disease models

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(14)

Published: May 16, 2024

Emerging evidence has linked the dysregulation of N6-methyladenosine (m6A) modification to inflammation and inflammatory diseases, but underlying mechanism still needs investigation. Here, we found that high levels m6A in a variety hyperinflammatory states are p65-dependent because Wilms tumor 1–associated protein (WTAP), key component "writer" complex, is transcriptionally regulated by p65, its overexpression can lead increased modification. Mechanistically, upregulated WTAP more prone phase separation facilitate aggregation writer complex nuclear speckles deposition marks on active transcripts, thereby accelerating proinflammatory response. Further, myeloid deficiency attenuates severity LPS-induced sepsis DSS-induced IBD. Thus, effect general risk-increasing mechanism, interrupting assembly reduce global targeting may be potential promising therapeutic strategy for alleviating hyperinflammation.

Language: Английский

---