RNA modification: mechanisms and therapeutic targets

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Aug. 24, 2023

Abstract RNA modifications are dynamic and reversible chemical on substrate that regulated by specific modifying enzymes. They play important roles in the regulation of many biological processes various diseases, such as development cancer other diseases. With help advanced sequencing technologies, role has caught increasing attention human diseases scientific research. In this review, we briefly summarized basic mechanisms several common modifications, including m6A, m5C, m1A, m7G, Ψ, A-to-I editing ac4C. Importantly, discussed their potential functions cancer, neurological disorders, cardiovascular metabolic genetic developmental well immune disorders. Through “writing-erasing-reading” mechanisms, regulate stability, translation, localization pivotal disease-related mRNAs to manipulate disease development. Moreover, also highlighted review all currently available RNA-modifier-targeting small molecular inhibitors or activators, most which designed against m6A-related enzymes, METTL3, FTO ALKBH5. This provides clues for clinical therapy future study directions modification field. More in-depth studies further activators needed a thorough understanding epitranscriptomics diagnosis, treatment, prognosis

Language: Английский

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cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 9, 2024

Abstract Background Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression organ degeneration, but the mechanism regulation of crosstalk network remain unclear. Main body abstract Cellular stress disrupts mitochondrial homeostasis, facilitates opening permeability transition pore leakage DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, subsequently induces activation onset pyroptosis. Meanwhile, inflammasome-associated protein caspase-1, Gasdermin D, CARD domain ASC potassium channel are involved in regulating pathway. Importantly, this has a cascade amplification effect that exacerbates immuno-inflammatory response, worsening pathological process autoimmune diseases. Given importance innate immunity, it is emerging new avenue explore mechanisms multiple disease pathogenesis. Therefore, efforts define strategies selectively modulate different settings have been or ongoing. In review, we will describe how mechanistic understanding driving possible therapeutics targeting network, focusing on interacting regulatory proteins, pathways, hub between inflammasomes, Short conclusion This review aims provide insight into roles pyroptosis, highlight some promising directions future research intervention.

Language: Английский

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Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

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Emerging role of RNA acetylation modification ac4C in diseases: Current advances and future challenges

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 213, P. 115628 - 115628

Published: May 27, 2023

Language: Английский

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NAT10 regulates the LPS-induced inflammatory response via the NOX2-ROS-NF-κB pathway in macrophages

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2023, Volume and Issue: 1870(7), P. 119521 - 119521

Published: June 10, 2023

Language: Английский

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Neutrophil extracellular traps contribute to immunothrombosis formation via the STING pathway in sepsis-associated lung injury

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 25, 2023

Neutrophil extracellular traps (NETs) are involved in the activation and dysfunction of multiple overlapping interacting pathways, including immune response to injury, inflammation, coagulation, which contribute pathogenesis sepsis-induced acute lung injury (SI-ALI). However, how NETs mediate relationship between inflammation coagulation has not been fully clarified. Here, we found that NETs, through stimulator interferon genes (STING) activation, induced endothelial cell damage with abundant production tissue factor (TF), magnified dysregulation inflammatory coagulant responses resulted poor prognosis SI-ALI model mice. Disruption inhibition STING improved outcomes septic mice reduced coagulation. Furthermore, Toll-like receptor 2 (TLR2) on surface cells was interaction pathway. Collectively, these findings demonstrate activate cascade a STING-dependent manner development SI-ALI.

Language: Английский

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NAT10 mediated ac4C acetylation driven m6A modification via involvement of YTHDC1-LDHA/PFKM regulates glycolysis and promotes osteosarcoma

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 17, 2024

Abstract The dynamic changes of RNA N6-methyladenosine (m 6 A) during cancer progression participate in various cellular processes. However, less is known about a possible direct connection between upstream regulator and m A modification, therefore affects oncogenic progression. Here, we have identified that key enzyme N4-acetylcytidine (ac4C) acetylation NAT10 highly expressed human osteosarcoma tissues, its knockdown enhanced contents significantly suppressed cell growth, migration invasion. Further results revealed silence inhibits mRNA stability translation reader protein YTHDC1, displayed an increase glucose uptake, decrease lactate production pyruvate content. YTHDC1 recognizes differential sites on enzymes glycolysis phosphofructokinase (PFKM) dehydrogenase (LDHA) mRNAs, which suppress pathway by increasing them methylation-dependent manner. partially abrogated the inhibitory effect caused tumor models vivo, lentiviral overexpression restored reduced depleting at level. Altogether, found ac4C driven modification can positively regulate cells reveals previously unrecognized signaling axis NAT10/ac4C-YTHDC1/m A-LDHA/PFKM osteosarcoma.

Language: Английский

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Advances in nanomaterial-targeted treatment of acute lung injury after burns

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 18, 2024

Abstract Acute lung injury ( ALI ) is a common complication in patients with severe burns and has complex pathogenesis high morbidity mortality rates. A variety of drugs have been identified the clinic for treatment ALI, but they toxic side effects caused by easy degradation body distribution throughout body. In recent years, as understanding mechanism underlying improved, scholars developed new nanomaterials that can be safely effectively targeted ALI. Most these methods involve such lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles other nanomaterials, which are to reach tissues perform their functions through active targeting passive targeting, process involves cells organelles. this review, first, mechanisms pathophysiological features occurrence after burn reviewed, potential therapeutic targets summarized, existing classified, possible problems challenges discussed provide reference development

Language: Английский

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Single‐Cell Landscape of Bronchoalveolar Lavage Fluid Identifies Specific Neutrophils during Septic Immunosuppression

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract Sepsis‐induced immunosuppression is related to increased susceptibility secondary infections and death. Lung the most vulnerable target organ in sepsis, but understanding of pulmonary state still limited. Here, single‐cell RNA sequencing bronchoalveolar lavage fluid (BALF) performed map landscape immune cells, revealing a neutrophil‐driven immunosuppressive program lungs patients with sepsis. Although genes are upregulated different only neutrophils dramatically increase BALF phase Five neutrophil subpopulations identified, among which CXCR2 + CD274 ( PD‐L1 coding gene) IL1RN significantly during septic immunosuppression. Interestingly, developmental trajectory from subpopulation disclosed. Moreover, therapeutic effect blockade observed on survival mice, along decreased number neutrophils. Taken together, discovered as contributor sepsis identified it potential treatment.

Language: Английский

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cGAS-STING targeting offers therapy choice in lung diseases

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 7, 2025

Cyclic GMP/AMP (cGAMP) synthase (cGAS), along with the endoplasmic reticulum (ER)-associated stimulator of interferon genes (STING), are crucial elements type 1 response. cGAS senses microbial DNA and self-DNA, labeling cGAS-STING as a mechanism in autoimmunity, sterile inflammatory responses, cellular senescence. However, chronic aberrant activation axis results autoimmune diseases. has emerged vital driving inflammation-related diseases, including lung Insights into biology pathway have enabled discovery small-molecule agents which potential to inhibit In this review, we first outline principal components signaling cascade. Then, discuss recent research that highlights general mechanisms by contributes focus on summarizing list bioactive compounds pathway, reviewing their mechanisms.These review novel groundbreaking therapeutic possibilities through targeting

Language: Английский

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