Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential

Biomolecules, Journal Year: 2022, Volume and Issue: 12(9), P. 1224 - 1224

Published: Sept. 2, 2022

Wilms’ tumor 1-associating protein (WTAP) is required for N6-methyladenosine (m6A) RNA methylation modifications, which regulate biological processes such as splicing, cell proliferation, cycle, and embryonic development. m6A the predominant form of mRNA modification in eukaryotes. WTAP exerts by binding to methyltransferase-like 3 (METTL3) nucleus METTL3-methyltransferase-like 14 (METTL14)-WTAP (MMW) complex, a core component methyltransferase complex (MTC), localizing nuclear patches. Studies have demonstrated that plays critical role various cancers, both dependent independent its methyltransferases. Here, we describe recent findings on structural features WTAP, mechanisms regulates functions, molecular functions cancers. By summarizing latest research, expect provide new directions insights oncology research discover targets cancer treatment.

Language: Английский

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Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 21, 2023

Abstract Cancer immunotherapy, especially immune checkpoint therapy, has revolutionized therapeutic options by reactivating the host system. However, efficacy varies, and only a small portion of patients develop sustained antitumor responses. Hence, illustrating novel strategies that improve clinical outcome therapy is urgently needed. N6-methyladenosine (m 6 A) been proved to be an efficient dynamic posttranscriptional modification process. It involved in numerous RNA processing, such as splicing, trafficking, translation degradation. Compelling evidence emphasizes paramount role m A regulation response. These findings may provide foundation for rational combination targeting checkpoints cancer treatment. In present review, we summarize current landscape biology, highlight latest on complex mechanisms which governs molecules. Furthermore, given critical immunity, discuss significance control.

Language: Английский

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N6-methyladenosine regulator YTHDF1 represses the CD8 + T cell-mediated antitumor immunity and ferroptosis in prostate cancer via m6A/PD-L1 manner

APOPTOSIS, Journal Year: 2023, Volume and Issue: 29(1-2), P. 142 - 153

Published: Sept. 12, 2023

Language: Английский

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ALKBH5‐Mediated RNA m⁶A Methylation Regulates the Migration, Invasion, and Proliferation of Rheumatoid Fibroblast‐Like Synoviocytes

Arthritis & Rheumatology, Journal Year: 2023, Volume and Issue: 76(2), P. 192 - 205

Published: Aug. 19, 2023

Objective Fibroblast‐like synoviocytes (FLSs) are critical for promoting joint damage in rheumatoid arthritis (RA). N 6 ‐methyladenosine (m A) modification plays key roles various diseases, but its role the pathogenesis of RA is largely unknown. Here, we investigate increased demethylase ALKBH5 promotion proliferation, migration, and invasion FLSs via regulating JARID2 expression. Methods expression was evaluated using real‐time quantitative polymerase chain reaction (RT‐qPCR) Western blot. 5‐ethynyl‐2′‐deoxyuridine, scratch wound healing, transwell assays were implemented to determine on FLS mobility, migration. Then, m A sequencing combined with RNA performed identify potential targets . immunoprecipitation pulldown then used validate interaction between protein messenger (mRNA). Collagen‐induced (CIA) delayed‐type hypersensitivity (DTHA) models further established assess therapeutic potency vivo. Results We demonstrated that synovium from RA. Functionally, knockdown inhibited FLSs, whereas overexpression displayed opposite effect. Mechanistically, mediated mRNA enhanced stability cooperation IGF2BP3 Intriguingly, severity attenuated mice DTHA knockout or rats CIA intra‐articular injection short hairpin RNA. Conclusion Our findings suggest ‐mediated crucial synovial hyperplasia might be a target even dysregulated fibroblasts wide range diseases. image

Language: Английский

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Hsa-LINC02418/mmu-4930573I07Rik regulated by METTL3 dictates anti-PD-L1 immunotherapeutic efficacy via enhancement of Trim21-mediated PD-L1 ubiquitination

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(12), P. e007415 - e007415

Published: Dec. 1, 2023

Background Limited response to programmed death ligand-1 (PD-L1)/programmed 1 (PD-1) immunotherapy is a major hindrance of checkpoint in non-small cell lung cancer (NSCLC). The abundance PD-L1 on the tumor surface crucial for responsiveness PD-1/PD-L1 immunotherapy. However, negative control expression and physiological significance inhibition NSCLC remain obscure. Methods Bioinformatics analysis was performed profile investigate long non-coding RNAs that negatively correlated with positively CD8+T infiltration NSCLC. Immunofluorescence, vitro PD-1 binding assay, T cell-induced apoptosis assays vivo syngeneic mouse models were used functional roles LINC02418 mmu-4930573I07Rik regulating anti-PD-L1 therapeutic efficacy molecular mechanism LINC02418-enhanced downregulation explored by immunoprecipitation, RNA immunoprecipitation (RIP), ubiquitination assays. RIP, luciferase reporter, messenger degradation m6A modification or expression. immunohistochemistry (IHC) verification determine LINC02418, infiltration. Results regulator infiltration, predicting favorable clinical outcomes patients downregulates enhancing mediated E3 ligase Trim21. Both hsa-LINC02418 (its homologous mice) regulate via Trim21, inducing . Furthermore, METTL3 N6-methyladenosine (m6A) YTHDF2 reader upregulates mmu-4930573I07Rik. In NSCLC, inversely Conclusion functions as cells promoting through ubiquitin-proteasome pathway. regulated METTL3/YTHDF2-mediated modification. This study illuminates underlying mechanisms regulation presents promising target improving effectiveness therapy

Language: Английский

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