Advanced Materials, Год журнала: 2023, Номер 36(9)
Опубликована: Дек. 8, 2023
Immunotherapy using an immune-checkpoint blockade has significantly improved its therapeutic effects. CM-272, which is a novel epigenetic inhibitor of G9a, induces immunogenic cell death (ICD) for recovering the sensitivity to anti-PD-1 antibodies; however, efficacy CM-272 greatly limited by promoting transcription activity HIF-1α form hypoxic environment. Here, Fe
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)
Опубликована: Сен. 22, 2022
RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.
Язык: Английский
Процитировано
194
Nature Communications, Год журнала: 2023, Номер 14(1)
Опубликована: Окт. 20, 2023
Abstract Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that content significantly elevated gastric (GC), especially malignant tumors. Screening reveals METTL16, an atypical methyltransferase, critical mediator through m 6 A modification on FDX1 mRNA. Furthermore, stress promotes METTL16 lactylation at site K229 followed cuproptosis. The process inhibited SIRT2. Elevated improves therapeutic efficacy ionophore– elesclomol. Combining elesclomol with AGK2, SIRT2-specific inhibitor, induce vitro vivo. These results reveal significance non-histone protein Given lactate concentrations GC, induction becomes promising strategy for GC.
Язык: Английский
Процитировано
143
Cell Death and Disease, Год журнала: 2023, Номер 14(2)
Опубликована: Фев. 27, 2023
Abstract Necroptosis refers to a regulated form of cell death induced by variety stimuli. Although it has been implicated in the pathogenesis many diseases, there is evidence support that necroptosis not purely detrimental process. We propose “double-edged sword” terms physiology and pathology. On one hand, can trigger an uncontrolled inflammatory cascade response, resulting severe tissue injury, disease chronicity, even tumor progression. other functions as host defense mechanism, exerting antipathogenic antitumor effects through its powerful pro-inflammatory properties. Moreover, plays important role during both development regeneration. Misestimation multifaceted features may influence therapeutic approaches targeting necroptosis. In this review, we summarize current knowledge pathways involved well five steps determine occurrence. The dual physiological pathological conditions also highlighted. Future studies strategies should fully consider complicated properties type death.
Язык: Английский
Процитировано
83
Molecular Cancer, Год журнала: 2023, Номер 22(1)
Опубликована: Июнь 30, 2023
Divergent N6-methyladenosine (m6A) modifications are dynamic and reversible posttranscriptional RNA that mediated by m6A regulators or methylation regulators, i.e., methyltransferases ("writers"), demethylases ("erasers"), m6A-binding proteins ("readers"). Aberrant associated with cancer occurrence, development, progression, prognosis. Numerous studies have established aberrant function as either tumor suppressors oncogenes in multiple types. However, the functions mechanisms of remain largely elusive should be explored. Emerging suggest can modulated epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, lactylation via noncoding action, cancer. This review summarizes current roles The for modification genesis segregated. will improve understanding regulatory regulators.
Язык: Английский
Процитировано
80
Advanced Science, Год журнала: 2024, Номер 11(13)
Опубликована: Янв. 21, 2024
Abstract N6‐methyladenosine (m 6 A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion angiogenesis are characteristic features of its TME. The role YTH RNA binding protein 2 (YTHDF2), as an m A reader, in regulating HCC TME not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 27 acetylation promoter region YTHDF2 enhanced expression HCC, upregulated predicted a worse prognosis. Animal experiments demonstrated Ythdf2 depletion inhibited spontaneous formation, while overexpression promoted xenografted progression. Mechanistically, recognized 5′‐untranslational ETS variant transcription factor 5 (ETV5) mRNA recruited eukaryotic translation initiation 3 subunit B to facilitate translation. Elevated ETV5 induced programmed death ligand‐1 vascular endothelial growth A, thereby promoting angiogenesis. Targeting via small interference RNA‐containing aptamer/liposomes successfully both Together, this findings reveal potential application prognosis targeted treatment.
Язык: Английский
Процитировано
26
MedComm, Год журнала: 2024, Номер 5(5)
Опубликована: Май 1, 2024
Abstract RNA modification, especially methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all modifications. It plays significant role in metabolism, affecting processing, stability, translation, thereby modulating gene expression cell essential proliferation, survival, metastasis. Increasing studies have revealed the disruption metabolism mediated by methylation has been implicated various aspects cancer particularly metabolic reprogramming immunity. This profound implications tumor growth, metastasis, therapy response. Herein, we elucidate fundamental characteristics their impact on expression. We highlight intricate relationship between reprogramming, immunity, using well‐characterized phenomenon as framework to discuss methylation's specific roles mechanisms progression. Furthermore, explore potential targeting regulators novel approach therapy. By underscoring complex which contributes this review provides foundation developing new prognostic markers therapeutic strategies aimed at treatment.
Язык: Английский
Процитировано
17
Advanced Science, Год журнала: 2024, Номер 11(13)
Опубликована: Янв. 22, 2024
Abstract Although immunogenic cell death (ICD) inducers evidently enhance the effectiveness of immunotherapy, their potential is increasingly restricted by development apoptosis resistance in tumor cells, poor immunogenicity, and low T‐cell immune responsiveness. In this study, for first time, piezoelectrically catalyzed Mg 2+ ‐doped hydroxyapatite (Mg‐HAP) nanoparticles, which are coated with a mesoporous silica layer loaded ONC201 as an agonist to specifically target receptor DR5 on ultimately developing Mg‐HAP@MS/ONC201 nanoparticle (MHMO NP) system, engineered. Owing its excellent piezoelectric properties, MHMO facilitates release significant amount reactive oxygen species Ca within effectively promoting upregulation expression inducing necroptosis overcome resistance. Concurrently, released microenvironment promotes CD8 + T activation response antitumor reaction induced ICD. Using RNA‐seq analysis, it elucidated that can activate NF‐κB pathway under catalysis, thus M1‐type macrophage polarization. summary, dual‐targeting therapy system targets both cells catalysis designed. This holds substantial advancements immunotherapy.
Язык: Английский
Процитировано
16
Lipids in Health and Disease, Год журнала: 2025, Номер 24(1)
Опубликована: Янв. 31, 2025
Язык: Английский
Процитировано
2
Redox Biology, Год журнала: 2022, Номер 58, С. 102546 - 102546
Опубликована: Ноя. 19, 2022
Язык: Английский
Процитировано
61
Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)
Опубликована: Июль 6, 2022
Abstract The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, immunosuppression. One the most common RNA N6-methyladenosine (m 6 A) methylation, widely involved regulation physiological pathological processes, including development. Compelling evidence indicates that m A methylation regulates transcription protein expression through shearing, export, translation, processing, thereby participating dynamic evolution TME. Specifically, methylation-mediated adaptation to phenotypic shift immune cells synergistically promote formation an immunosuppressive supports proliferation metastasis. In this review, we have focused on involvement tumor-adaptive described detailed linking change cell biological functions. view collective data, advocate treating as complete ecosystem components crosstalk with each other achieve adaptive changes. Finally, describe potential utility methylation-targeted therapies immunotherapy clinical applications challenges faced, aim advancing research.
Язык: Английский
Процитировано
59