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Cell Death & Disease Mar 2021The innate and adaptive immune cells have complex signaling pathways for sensing and initiating immune responses against disease. These pathways are interrupted at... (Review)
Review
The innate and adaptive immune cells have complex signaling pathways for sensing and initiating immune responses against disease. These pathways are interrupted at different levels to occur immune evasion, including by N6-methyladenosine (m6A) modification. In this review, we discuss studies revealing the immune evasion mechanism by m6A modification, which underlies the retouching of these signaling networks and the rapid tolerance of innate and adaptive immune molecules during disease. We also focus on the functions of m6A in main chemokines regulation, and their roles in promotive and suppressive immune cell recruitment. We then discuss some of the current challenges in the field and describe future directions for the immunological mechanisms of m6A modification.
Topics: Adenosine; Disease Progression; Humans; Immune Evasion; RNA
PubMed: 33741904
DOI: 10.1038/s41419-021-03585-z -
Cell Proliferation Oct 2022Musculoskeletal disorder (MSD) are a class of inflammatory and degener-ative diseases, but the precise molecular mechanisms are still poorly understood. Noncoding RNA... (Review)
Review
BACKGROUND
Musculoskeletal disorder (MSD) are a class of inflammatory and degener-ative diseases, but the precise molecular mechanisms are still poorly understood. Noncoding RNA (ncRNA) N6-methyladenosine (m6A) modification plays an essential role in the pathophysiological process of MSD. This review summarized the interaction between m6A RNA methylation and ncRNAs in the molecular regulatory mechanism of MSD. It provides a new perspective for the pathophysiological mechanism and ncRNA m6A targeted therapy of MSD.
METHODS
A comprehensive search of databases was conducted with musculoskeletal disorders, noncoding RNA, N6-methyladenosine, intervertebral disc degeneration, osteoporosis, osteosarcoma, osteoarthritis, skeletal muscle, bone, and cartilage as the key-words. Then, summarized all the relevant articles.
RESULTS
Intervertebral disc degeneration (IDD), osteoporosis (OP), osteosarcoma (OS), and osteoarthritis (OA) are common MSDs that affect muscle, bone, cartilage, and joint, leading to limited movement, pain, and disability. However, the precise pathogenesis remains unclear, and no effective treatment and drug is available at present. Numerous studies confirmed that the mutual regulation between m6A and ncRNAs (i.e., microRNAs, long ncRNAs, and circular RNAs) was found in MSD, m6A modification can regulate ncRNAs, and ncRNAs can also target m6A regulators. ncRNA m6A modification plays an essential role in the pathophysiological process of MSDs by regulating the homeostasis of skeletal muscle, bone, and cartilage.
CONCLUSION
m6A interacts with ncRNAs to regulate multiple biological processes and plays important roles in IDD, OP, OS, and OA. These studies provide new insights into the pathophysiological mechanism of MSD and targeting m6A-modified ncRNAs may be a promising therapy approach.
Topics: Adenosine; Bone Neoplasms; Humans; Intervertebral Disc Degeneration; Methylation; MicroRNAs; Osteoarthritis; Osteoporosis; Osteosarcoma; RNA, Circular; RNA, Long Noncoding; RNA, Untranslated
PubMed: 35735243
DOI: 10.1111/cpr.13294 -
International Journal of Molecular... Nov 2021A key objective in immuno-oncology is to reactivate the dormant immune system and increase tumour immunogenicity. Adenosine is an omnipresent purine that is formed in... (Review)
Review
A key objective in immuno-oncology is to reactivate the dormant immune system and increase tumour immunogenicity. Adenosine is an omnipresent purine that is formed in response to stress stimuli in order to restore physiological balance, mainly via anti-inflammatory, tissue-protective, and anti-nociceptive mechanisms. Adenosine overproduction occurs in all stages of tumorigenesis, from the initial inflammation/local tissue damage to the precancerous niche and the developed tumour, making the adenosinergic pathway an attractive but challenging therapeutic target. Many current efforts in immuno-oncology are focused on restoring immunosurveillance, largely by blocking adenosine-producing enzymes in the tumour microenvironment (TME) and adenosine receptors on immune cells either alone or combined with chemotherapy and/or immunotherapy. However, the effects of adenosinergic immunotherapy are not restricted to immune cells; other cells in the TME including cancer and stromal cells are also affected. Here we summarise recent advancements in the understanding of the tumour adenosinergic system and highlight the impact of current and prospective immunomodulatory therapies on other cell types within the TME, focusing on adenosine receptors in tumour cells. In addition, we evaluate the structure- and context-related limitations of targeting this pathway and highlight avenues that could possibly be exploited in future adenosinergic therapies.
Topics: Adenosine; Animals; Carcinogenesis; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasms; Receptors, Purinergic P1; Tumor Microenvironment
PubMed: 34830449
DOI: 10.3390/ijms222212569 -
Circulation Oct 2008Ischemic injury to the myocardium is a leading cause of morbidity and mortality around the globe. It is worth remembering, however, that this insult to the heart emerged...
Ischemic injury to the myocardium is a leading cause of morbidity and mortality around the globe. It is worth remembering, however, that this insult to the heart emerged only in the last few centuries, an instant in time from an evolutionary perspective. Thus, any cardioprotective responses to ischemic injury undoubtedly evolved for an entirely different purpose. Beyond pure academic interest, however, there is a profound clinical need to identify new means of protecting the myocardium from disease-related stress. Among the strategies in development is a concerted effort to understand and enhance the body’s innate mechanisms of cardioprotection.
Topics: Adenosine; Adenosine A3 Receptor Agonists; Animals; Cardiotonic Agents; Cardiovascular Diseases; Humans; Receptor, Adenosine A3
PubMed: 18936336
DOI: 10.1161/CIRCULATIONAHA.108.810101 -
Journal of Cardiothoracic Surgery Dec 2022Despite the rise in morbidity and mortality associated with vascular diseases, the underlying pathophysiological molecular mechanisms are still unclear. RNA... (Review)
Review
Despite the rise in morbidity and mortality associated with vascular diseases, the underlying pathophysiological molecular mechanisms are still unclear. RNA N6-methyladenosine modification, as the most common cellular mechanism of RNA regulation, participates in a variety of biological functions and plays an important role in epigenetics. A large amount of evidence shows that RNA N6-methyladenosine modifications play a key role in the morbidity caused by vascular diseases. Further research on the relationship between RNA N6-methyladenosine modifications and vascular diseases is necessary to understand disease mechanisms at the gene level and to provide new tools for diagnosis and treatment. In this study, we summarize the currently available data on RNA N6-methyladenosine modifications in vascular diseases, addressing four aspects: the cellular regulatory system of N6-methyladenosine methylation, N6-methyladenosine modifications in risk factors for vascular disease, N6-methyladenosine modifications in vascular diseases, and techniques for the detection of N6-methyladenosine-methylated RNA.
Topics: Humans; Methylation; RNA; Adenosine; Vascular Diseases
PubMed: 36536469
DOI: 10.1186/s13019-022-02077-1 -
Advances in Virus Research 2022Methylation at the N-position of either adenosine (mA) or 2'-O-methyladenosine (mAm) represents two of the most abundant internal modifications of coding and non-coding... (Review)
Review
Methylation at the N-position of either adenosine (mA) or 2'-O-methyladenosine (mAm) represents two of the most abundant internal modifications of coding and non-coding RNAs, influencing their maturation, stability and function. Additionally, although less abundant and less well-studied, monomethylation at the N-position (mA) can have profound effects on RNA folding. It has been known for several decades that RNAs produced by both DNA and RNA viruses can be mA/mAm modified and the list continues to broaden through advances in detection technologies and identification of the relevant methyltransferases. Recent studies have uncovered varied mechanisms used by viruses to manipulate the mA pathway in particular, either to enhance virus replication or to antagonize host antiviral defenses. As such, RNA modifications represent an important frontier of exploration in the broader realm of virus-host interactions, and this new knowledge already suggests exciting opportunities for therapeutic intervention. In this review we summarize the principal mechanisms by which mA/mAm can promote or hinder viral replication, describe how the pathway is actively manipulated by biomedically important viruses, and highlight some remaining gaps in understanding how adenosine methylation of RNA controls viral replication and pathogenesis.
Topics: Adenosine; Animals; Methylation; RNA; Virus Replication; Viruses
PubMed: 35840182
DOI: 10.1016/bs.aivir.2022.01.002 -
British Journal of Sports Medicine Mar 1992By influencing the regulation of the mechanisms of angiogenesis, erythropoietin production, blood flow, myocardial glucose uptake, glycogenolysis, systolic blood... (Review)
Review
By influencing the regulation of the mechanisms of angiogenesis, erythropoietin production, blood flow, myocardial glucose uptake, glycogenolysis, systolic blood pressure, respiration, plasma norepinephrine and epinephrine levels, adenosine may exert a significant effect on the body's adaptation response to exercise. However, adenosine's possible influence over the vasodilatory response to exercise in skeletal muscle is controversial and more research is required to resolve this issue. Various popular exercise training methods, such as cyclic training, interval training, and the 'warm down' from training may increase adenosine levels and thereby might enhance the response of adenosine-influenced adaptive mechanisms. Among the several classes of drugs which may enhance extracellular adenosine levels and thereby might augment adenosine-influenced adaptive mechanisms, are the anabolic steroidal and some readily available non-steroidal anti-inflammatory drugs (NSAIDs).
Topics: Adaptation, Physiological; Adenosine; Anabolic Agents; Anti-Inflammatory Agents, Non-Steroidal; Exercise; Humans; Physical Education and Training
PubMed: 1600457
DOI: 10.1136/bjsm.26.1.54 -
Journal of Neurochemistry Oct 2018Research over the past decade has provided strong support for the importance of various epigenetic mechanisms, including DNA and histone modifications in regulating... (Review)
Review
Research over the past decade has provided strong support for the importance of various epigenetic mechanisms, including DNA and histone modifications in regulating activity-dependent gene expression in the mammalian central nervous system. More recently, the emerging field of epitranscriptomics revealed an equally important role of post-transcriptional RNA modifications in shaping the transcriptomic landscape of the brain. This review will focus on the methylation of the adenosine base at the N6 position, termed N methyladenosine (m6A), which is the most abundant internal modification that decorates eukaryotic messenger RNAs. Given its prevalence and dynamic regulation in the adult brain, the m6A-epitranscriptome provides an additional layer of regulation on RNA that can be controlled in a context- and stimulus-dependent manner. Conceptually, m6A serves as a molecular switch that regulates various aspects of RNA function, including splicing, stability, localization, or translational control. The versatility of m6A function is typically determined through interaction or disengagement with specific classes of m6A-interacting proteins. Here we review recent advances in the field and provide insights into the roles of m6A in regulating brain function, from development to synaptic plasticity, learning, and memory. We also discuss how aberrant m6A signaling may contribute to neurodevelopmental and neuropsychiatric disorders.
Topics: Adenosine; Animals; Brain; Epigenomics; Humans; Neurobiology; Neuronal Plasticity; Protein Processing, Post-Translational
PubMed: 29873074
DOI: 10.1111/jnc.14481 -
Genomics, Proteomics & Bioinformatics Apr 2018Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated... (Review)
Review
Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N-methyladenosine (mA) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, mA can be incorporated by a methyltransferase complex and removed by demethylases, which ensures that the mA modification is reversible and dynamic. Moreover, mA is recognized by the YT521-B homology (YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the mA recognition by YTH domain-containing proteins, which would shed new light on mA-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.
Topics: Adenosine; Animals; Humans; Protein Binding; Protein Domains; RNA; RNA-Binding Proteins
PubMed: 29715522
DOI: 10.1016/j.gpb.2018.04.002 -
Journal of Experimental & Clinical... Apr 2021The N6-methyladenosine (m6A) modification is a dynamic and reversible epigenetic modification, which is co-transcriptionally deposited by a methyltransferase complex,... (Review)
Review
The N6-methyladenosine (m6A) modification is a dynamic and reversible epigenetic modification, which is co-transcriptionally deposited by a methyltransferase complex, removed by a demethylase, and recognized by reader proteins. Mechanistically, m6A modification regulates the expression levels of mRNA and nocoding RNA by modulating the fate of modified RNA molecules, such as RNA splicing, nuclear transport, translation, and stability. Several studies have shown that m6A modification is dysregulated in the progression of multiple diseases, especially human tumors. We emphasized that the dysregulation of m6A modification affects different signal transduction pathways and involves in the biological processes underlying tumor cell proliferation, apoptosis, invasion and migration, and metabolic reprogramming, and discuss the effects on different cancer treatment.
Topics: Adenosine; Disease Progression; Humans; Neoplasms; Signal Transduction
PubMed: 33926508
DOI: 10.1186/s13046-021-01952-4