Human Cell, Journal Year: 2025, Volume and Issue: 38(2)
Published: Jan. 3, 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
96
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
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
Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)
Published: July 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.
Language: Английский
Citations
60
Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)
Published: Aug. 27, 2022
Neutrophil extracellular traps (NETs) assist pathogen clearance, while excessive NETs formation is associated with exacerbated inflammatory responses and tissue injury in acute lung (ALI)/acute respiratory distress syndrome (ARDS). Autophagy generally considered to be a protective process, but autophagy dysfunction harmful. Whether how affect autophagic flux during sepsis-induced ALI are currently unknown. Here, we confirmed that the level of was increased ARDS patients mice models, which led impairment deterioration disease. Mechanistically, activated METTL3 mediated m6A methylation Sirt1 mRNA alveolar epithelial cells, resulting abnormal autophagy. These findings provide new insights into contribute development sepsis-associated ALI/ARDS.
Language: Английский
Citations
60