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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Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 1, 2024

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment advanced HCC, but problems such as drug resistance immune-related adverse events still exist in clinical practice. immunosuppressive tumor microenvironment (TME) HCC restricts efficacy essential for progression metastasis. Therefore, it necessary to elucidate mechanisms behind TME develop apply immunotherapy. This review systematically summarizes pathogenesis formation TME, by which accelerates We also status further discuss existing challenges potential therapeutic strategies targeting TME. hope inspire optimizing innovating immunotherapeutic comprehensively understanding structure function HCC.

Language: Английский

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METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 24, 2024

Abstract Background RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m 7 G) modification and its modifiers METTL1/WDR4 confirmed an oncogene role multiple cancers. However, the functions molecular mechanisms of acute myeloid leukemia (AML) remain be determined. Methods expression levels were quantified using qRT-PCR, western blot analysis on AML clinical samples, bioinformatics publicly available datasets. CCK-8 assays cell count performed determine proliferation. Flow cytometry conducted assess cycle apoptosis rates. Multiple techniques used for mechanism studies vitro assays, such as northern blotting, liquid chromatography-coupled mass spectrometry (LC–MS/MS), tRNA stability analysis, transcriptome sequencing, small non-coding quantitative proteomics, protein synthesis measurements. Results are significantly elevated patients associated with poor prognosis. METTL1 knockdown resulted reduced proliferation increased cells. Mechanically, leads significant decrease m G abundance tRNA, which further destabilizes tRNAs facilitates biogenesis tsRNAs In addition, profiling nascent proteins revealed that transfection total isolated from cells decreased global translation efficiency Conclusions Taken together, our study demonstrates important leukaemogenesis, provides a promising target candidate therapy.

Language: Английский

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Effects of DNA, RNA, and Protein Methylation on the Regulation of Ferroptosis

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(11), P. 3558 - 3575

Published: Jan. 1, 2023

Ferroptosis is a form of programmed cell death characterized by elevated intracellular ferrous ion levels and increased lipid peroxidation.Since its discovery characterization in 2012, considerable progress has been made understanding the regulatory mechanisms pathophysiological functions ferroptosis.Recent findings suggest that numerous organ injuries (e.g., ischemia/reperfusion injury) degenerative pathologies aortic dissection neurodegenerative disease) are driven ferroptosis.Conversely, insufficient ferroptosis linked to tumorigenesis.Furthermore, recent study revealed effect on hematopoietic stem cells under physiological conditions.The identified date include mainly iron metabolism, such as transport ferritinophagy, redox systems, glutathione peroxidase 4 (GPX4)-glutathione (GSH), ferroptosis-suppressor-protein 1 (FSP1)-CoQ10, FSP1-vitamin K (VK), dihydroorotate dehydrogenase (DHODH)-CoQ, GTP cyclohydrolase (GCH1)-tetrahydrobiopterin (BH4).Recently, an increasing number studies have demonstrated important role played epigenetic mechanisms, especially DNA, RNA, protein methylation, ferroptosis.In this review, we provide critical analysis molecular networks date, with focus methylation.Furthermore, discuss some debated unanswered questions should be foci future research field.

Language: Английский

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POP1 Facilitates Proliferation in Triple-Negative Breast Cancer via m6A-Dependent Degradation of CDKN1A mRNA

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Triple-negative breast cancer (TNBC) is currently the worst prognostic subtype of cancer, and there no effective treatment other than chemotherapy. Processing precursors 1 (POP1) most substantially up-regulated RNA-binding protein (RBP) in TNBC. However, role POP1 TNBC remains clarified. A series molecular biological experiments vitro vivo clinical correlation analyses were conducted to clarify function regulatory mechanism Here, we identified that significantly associated with poor prognosis. We further demonstrate promotes cell cycle proliferation vivo. Mechanistically, directly binds coding sequence (CDS) region CDKN1A mRNA degrades it. The degradation process depends on N6-methyladenosine (m6A) modification at 497th site recognition this by YTH RNA binding 2 (YTHDF2). Moreover, m6A inhibitor STM2457 potently impaired POP1-overexpressed cells improved sensitivity paclitaxel. In summary, our findings reveal pivotal promoting degrading inhibition a promising therapeutic strategy for

Language: Английский

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Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 22, 2024

Abstract Cancer immunotherapy has emerged as a promising strategy in the treatment of colorectal cancer, and relapse after tumor attracted increasing attention. stem cells (CSCs), small subset with self-renewal differentiation capacities, are resistant to traditional therapies such radiotherapy chemotherapy. Recently, CSCs have been proven be driving immunotherapy. However, mutual interactions between cancer niche immune largely uncharacterized. In this review, we focus on CSCs, CSC-immune cell CSC-based Colorectal characterized by robust expression surface markers CD44, CD133 Lgr5; hyperactivation stemness-related signaling pathways, Wnt/β-catenin, Hippo/Yap1, Jak/Stat Notch pathways; disordered epigenetic modifications, including DNA methylation, histone modification, chromatin remodeling, noncoding RNA action. Moreover, express abnormal levels immune-related genes MHC checkpoint molecules mutually interact multiple tumorigenesis-related processes, initiation, maintenance, metastasis drug resistance. To date, many targeting evaluated, monoclonal antibodies, antibody‒drug conjugates, bispecific vaccines adoptive therapy, molecule inhibitors. With development CSC-/niche-targeting technology, well integration multidisciplinary studies, novel that eliminate reverse their immunosuppressive microenvironment expected developed for solid tumors, cancer.

Language: Английский

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Emerging role of RNA modification and long noncoding RNA interaction in cancer

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(6), P. 816 - 830

Published: Feb. 14, 2024

Abstract RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence progression of cancer through multiple pathways. The function expression these epigenetic regulators have gradually become a hot topic research. Mutation regulation noncoding RNA, lncRNA, play major role cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions its dysregulation can promote tumor metastasis. In this review, we summarize modifications lncRNAs. Furthermore, discuss relationship between modification lncRNA interaction various cancers. Therefore, review gives comprehensive understanding mechanisms by which affects cancers regulating lncRNAs, may shed new light on research provide insights into therapy.

Language: Английский

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Foot-and-mouth disease virus VP1 degrades YTHDF2 through autophagy to regulate IRF3 activity for viral replication

Autophagy, Journal Year: 2024, Volume and Issue: 20(7), P. 1597 - 1615

Published: March 22, 2024

Many viruses, including foot-and-mouth disease virus (FMDV), can promote the degradation of host proteins through macroautophagy/autophagy, thereby promoting viral replication. However, regulatory mechanism between autophagy and innate immune responses is not fully understood during FMDV infection. Here, we found that GTPBP4/NOG1 (GTP binding protein 4) a negative regulator responses. GTPBP4 deficiency promotes antiviral response, resulting in ability to Meanwhile, GTPBP4-deficient mice are more resistant To antagonize host's immunity, structural VP1 expression GTPBP4, 209th site responsible for this effect. Mechanically, infection interacts with degrades YTHDF2 (YTH N6-methyladenosine RNA F2) an AKT-MTOR-dependent pathway, increase mRNA levels. Increased inhibits IRF3 Ifnb/Ifn-β promoter, suppressing FMDV-induced type I interferon production. In conclusion, our study revealed underlying how negatively regulates immunity which would contribute understanding regulation function

Language: Английский

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A systematic review of epigenetic interplay in kidney diseases: Crosstalk between long noncoding RNAs and methylation, acetylation of chromatin and histone

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116922 - 116922

Published: June 13, 2024

The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation acetylation offer new perspectives on the pathogenesis treatment of kidney diseases. lncRNAs, a class transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized key regulatory molecules influencing gene expression through diverse mechanisms. They modulate by recruiting or blocking enzymes responsible for adding removing methyl acetyl groups, DNA, N6-methyladenosine (m6A) histone acetylation, subsequently altering chromatin structure accessibility. In diseases acute injury (AKI), chronic disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), renal cell carcinoma (RCC), aberrant patterns DNA/RNA/histone have been associated onset progression, revealing complex interplay lncRNA dynamics. Recent studies highlighted how lncRNAs can impact pathology affecting function genes involved in cycle control, fibrosis, inflammatory responses. This review will separately address roles diseases, particular emphasis elucidating bidirectional effects underlying mechanisms conjunction addition to potential exacerbating renoprotective pathologies. Understanding reciprocal relationships not only shed light molecular underpinnings pathologies but also present avenues therapeutic interventions biomarker development, advancing precision medicine nephrology.

Language: Английский

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hnRNPU-mediated pathogenic alternative splicing drives gastric cancer progression

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 7, 2025

Abstract Background Alternative splicing (AS) is a process that facilitates the differential inclusion of exonic sequences from precursor messenger RNAs, significantly enhancing diversity transcriptome and proteome. In cancer, pathogenic AS events are closely related to cancer progression. This study aims investigate role regulatory mechanisms in gastric (GC). Methods We analyzed various tumor samples identified hnRNPU as key factor GC. The effects on progression were assessed through vitro vivo experiments. Gene knockout models FTO inhibitor (meclofenamic acid) used validate interaction between their impact AS. Results found serves GC, its high expression associated with poor clinical prognosis. Genetic depletion reduced GC Mechanistically, m 6 A demethylase interacts transcripts, decreasing modification levels hnRNPU, which leads exon 14 skipping MET gene, thereby promoting meclofenamic acid effectively inhibited cell growth both vivo. Conclusion FTO/hnRNPU axis induces aberrant MET, growth. Targeting may interfere abnormal provide potential diagnostic therapeutic strategy for Graphical Schematic model findings this work: Aberrant binds FTO. A-modified transcripts recognized by reader YTHDF3 subsequently demethylated demethylation enhances stability mRNA, consequently alternative MET. altered pattern ultimately contributes proliferation cells.

Language: Английский

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