Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106811 - 106811
Published: Jan. 1, 2025
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)
Published: Sept. 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.
Language: Английский
Citations
205
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: Oct. 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.
Language: Английский
Citations
159
Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)
Published: Feb. 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.
Language: Английский
Citations
92
Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)
Published: June 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.
Language: Английский
Citations
85
Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)
Published: Jan. 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.
Language: Английский
Citations
26
Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)
Published: Jan. 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.
Language: Английский
Citations
17
MedComm, Journal Year: 2024, Volume and Issue: 5(5)
Published: May 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.
Language: Английский
Citations
17
Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)
Published: Jan. 31, 2025
Language: Английский
Citations
2
Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 247 - 247
Published: Feb. 8, 2025
N6-methyladenosine (m6A) is the most prevalent internal chemical modification in eukaryotic messenger RNA (mRNA), significantly impacting its lifecycle through dynamic and reversible processes involving methyltransferase, demethylase, binding proteins. These regulate mRNA stability, splicing, nuclear export, translation, degradation. Programmed cell death (PCD), a tightly controlled process encompassing apoptosis, pyroptosis, ferroptosis, autophagy, necroptosis, plays crucial role maintaining cellular homeostasis, tissue development, function. Recently, m6A has emerged as significant research area due to regulating PCD implications cardiovascular diseases (CVDs). In this review, we delve into intricate relationship between various types modification, emphasizing their pivotal roles initiation progression of CVDs such myocardial ischemia-reperfusion (I/R), atherosclerosis (AS), pulmonary hypertension (PH), cardiomyopathy, doxorubicin (Dox)-induced cardiotoxicity (DIC), heart failure (HF), infarction (MI). Our findings underscore potential elucidating CVD pave new pathways for prevention treatment strategies.
Language: Английский
Citations
2
Redox Biology, Journal Year: 2022, Volume and Issue: 58, P. 102546 - 102546
Published: Nov. 19, 2022
Language: Английский
Citations
64