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Journal of Cellular Physiology Sep 2022N6-methyladenosine (m6A) modification is one of the most abundant modifications in eukaryotic mRNA, regulated by m6A methyltransferase and demethylase. m6A modified RNA... (Review)
Review
N6-methyladenosine (m6A) modification is one of the most abundant modifications in eukaryotic mRNA, regulated by m6A methyltransferase and demethylase. m6A modified RNA is specifically recognized and bound by m6A recognition proteins, which mediate splicing, maturation, exonucleation, degradation, and translation. In gynecologic malignancies, m6A RNA modification-related molecules are expressed aberrantly, significantly altering the posttranscriptional methylation level of the target genes and their stability. The m6A modification also regulates related metabolic pathways, thereby controlling tumor development. This review analyzes the composition and mode of action of m6A modification-related proteins and their biological functions in the malignant progression of gynecologic malignancies, which provide new ideas for the early clinical diagnosis and targeted therapy of gynecologic malignancies.
Topics: Adenosine; Female; Genital Neoplasms, Female; Humans; Methylation; RNA
PubMed: 35802474
DOI: 10.1002/jcp.30828 -
Drug Discovery Today Jun 2021In recent years, many studies have shown that adenosine has efficacy for treating cancer. More importantly, some adenosine analogs have been successfully marketed to... (Review)
Review
In recent years, many studies have shown that adenosine has efficacy for treating cancer. More importantly, some adenosine analogs have been successfully marketed to fulfill anticancer purposes. In this review, we summarize the anticancer effects of adenosine and its analogs in clinical trials and preclinical studies, with focus on their anticancer mechanisms. In addition, we link the anticancer activities of adenosine analogs with their structures through structure-activity relationship (SAR) analysis, and highlight additional promising anticancer drug candidates. We hope that this review will be of help in understanding the importance of adenosine and its analogs with anticancer activities and directing future research and development of such compounds.
Topics: Adenosine; Animals; Antineoplastic Agents; Drug Development; Humans; Neoplasms; Structure-Activity Relationship
PubMed: 33639248
DOI: 10.1016/j.drudis.2021.02.020 -
Zhongguo Fei Ai Za Zhi = Chinese... Jul 2022Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is... (Review)
Review
Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies. .
Topics: Adenosine; Adenosine A2 Receptor Antagonists; Humans; Lung Neoplasms; Receptor, Adenosine A2A; Tumor Microenvironment
PubMed: 35899442
DOI: 10.3779/j.issn.1009-3419.2022.102.24 -
Transcription Oct 2021RNA modifications are prevalent among all the classes of RNA, regulate diverse biological processes, and have emerged as a key regulatory mechanism in... (Review)
Review
RNA modifications are prevalent among all the classes of RNA, regulate diverse biological processes, and have emerged as a key regulatory mechanism in post-transcriptional control of gene expression. They are subjected to precise spatial and temporal control and shown to be critical for the maintenance of normal development and physiology. For example, mA modification of mRNA affects stability, recruitment of RNA binding protein (RBP), translation, and splicing. The deposition of m6A on the RNA happens co-transcriptionally, allowing the tight coupling between the transcription and RNA modification machinery. The mA modification is affected by transcriptional dynamics, but recent insights also suggest that mA machinery impacts transcription and chromatin signature.
Topics: Adenosine; Gene Expression Regulation; RNA; RNA Processing, Post-Transcriptional; RNA Splicing; RNA, Messenger
PubMed: 35380917
DOI: 10.1080/21541264.2022.2057177 -
Molecular Therapy : the Journal of the... Oct 2020Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide, despite marked improvements in prevention, diagnosis, and early intervention.... (Review)
Review
Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide, despite marked improvements in prevention, diagnosis, and early intervention. There is an urgent need to discover more effective therapeutic strategies, which would be facilitated by a more in-depth understanding of CVDs and their underlying molecular mechanisms. Recent advances in knowledge about epigenetic mechanisms, especially RNA methylation, have revealed a close relationship between epigenetic modifications and CVDs and have brought to potential novel targets for diagnosis and treatment. Here, we provide a review of recent studies exploring RNA N-methyladenosine (mA) modification, with particular emphasis on its role in CVDs, such as coronary heart disease, hypertension, cardiac hypertrophy, and heart failure. We also introduce the "life cycle" of mA and its dominant function in several biological processes. Finally, we highlight the prospects of treatment based on interfering with mA, which could have a transformative effect on clinical medicine.
Topics: Adenosine; Cardiovascular Diseases; Disease Susceptibility; Epigenesis, Genetic; Gene Expression Regulation; Humans; Methylation; Molecular Targeted Therapy; RNA
PubMed: 32910911
DOI: 10.1016/j.ymthe.2020.08.010 -
Journal of Cellular Physiology Mar 2022N -methyladenosine (m A), the sixth N methylation of adenylate (A) in RNA, is the most abundant transcriptome modification in eukaryotic messenger RNA (mRNAs). m A... (Review)
Review
N -methyladenosine (m A), the sixth N methylation of adenylate (A) in RNA, is the most abundant transcriptome modification in eukaryotic messenger RNA (mRNAs). m A modification exists in both coding mRNA and noncoding RNAs, and its functions are controlled by methyltransferase, demethylase, and m A reading proteins. Methylation modification of m A can regulate RNA cleavage, transport, stability, and expression. This review summarizes the enzymes involved in RNA m A methylation and the commonly used detection methods. The role of m A modification in physiological processes is described, and its impact on tumorigenesis, viral infection, and diabetes is further highlighted. Moreover, up-to-date knowledge of the implications of RNA m A modification in ocular diseases such as uveal melanoma and diabetic retinopathy is introduced. Clarifying the mechanism of RNA m A methylation will help elucidate the pathogenesis of various diseases, providing options for subsequent treatment.
Topics: Adenosine; Eye Diseases; Humans; Methylation; Methyltransferases; RNA; RNA, Messenger
PubMed: 34913163
DOI: 10.1002/jcp.30652 -
Cell Communication and Signaling : CCS Sep 2022N6-methyl-adenosine (mA) is the most prevalent modification on mRNAs and long noncoding RNAs (lnRNAs) in higher eukaryotes. Modulation of mA relies on mA writers,... (Review)
Review
N6-methyl-adenosine (mA) is the most prevalent modification on mRNAs and long noncoding RNAs (lnRNAs) in higher eukaryotes. Modulation of mA relies on mA writers, erasers and readers. mA modification contributes to diverse fundamental biological functions at the molecular, cellular, and physiological levels. The dysregulation of mA modification has been implicated in various human diseases. Thus, mA modification has now become a research hotspot for its potential therapeutic applications in the treatment of various cancers and diseases. The immune system is essential to provide defense against infections and cancers. This review summarizes the current knowledge about the roles of mA in regulating immune cell functions and immune responses. Video abstract.
Topics: Adenosine; Humans; Methylation; Methyltransferases; Neoplasms
PubMed: 36085064
DOI: 10.1186/s12964-022-00939-8 -
Cell Proliferation Jan 2022N6-Methyladenosine (m6A) is considered the most common and endogenous modification of eukaryotic RNAs. Highly conserved in many species, m6A regulates RNA metabolism,... (Review)
Review
N6-Methyladenosine (m6A) is considered the most common and endogenous modification of eukaryotic RNAs. Highly conserved in many species, m6A regulates RNA metabolism, cell differentiation, cell circadian rhythm, and cell cycle; it also responds to endogenous and exogenous stimuli and is associated with the development of tumors. The m6A methyltransferase complex (MTC) regulates the m6A modification of transcripts and involves two components, methyltransferase-like enzyme 3 (METTL3) and methyltransferase-like enzyme 14 (METTL14), and other auxiliary regulatory distinct components. Though with no catalytic effect, METTL14 serves as an RNA-binding scaffold in MTC, promotes RNA substrate recognition, activates, and escalates the catalytic capability of METTL3, thus accounting for a pivotal member of the complex. It was reported that METTL14 regulates tumor proliferation, metastasis, and self-renewal, and plays a part in tumorigenesis, tumor progression, and other processes. The present work is a review of the role of METTL14 both as a tumor suppressor and a tumor promoter in the oncogenesis and progression of various tumors, as well as the potential molecular mechanisms.
Topics: Adenosine; Animals; Genes, Tumor Suppressor; Humans; Methyltransferases; Neoplasms; Oncogenes; RNA
PubMed: 34904301
DOI: 10.1111/cpr.13168 -
Genes May 2022-methyladenosine (mA) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Recent studies based on technical advances... (Review)
Review
-methyladenosine (mA) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Recent studies based on technical advances in analytical chemistry and high-throughput sequencing methods have revealed the crucial roles of mA RNA modification in gene regulation and biological processes. In this review, we focus on progress in the study of mA methyltransferases, mA demethylases and mA-dependent RNA-binding proteins and highlight the biological mechanisms and functions of mA RNA modification, as well as its association with human disease. We also summarize the current understanding of detection approaches for mA RNA modification.
Topics: Adenosine; Gene Expression Regulation; Humans; Methylation; RNA Processing, Post-Transcriptional; RNA, Messenger
PubMed: 35627295
DOI: 10.3390/genes13050910 -
Biochimica Et Biophysica Acta. Reviews... Nov 2023As a new pillar of cancer therapy, tumor immunotherapy has brought irreplaceable durable responses in tumors. Considering its low response rate, additional immune... (Review)
Review
As a new pillar of cancer therapy, tumor immunotherapy has brought irreplaceable durable responses in tumors. Considering its low response rate, additional immune regulatory mechanisms will be critical for the development of next-generation immune therapeutics. As a key regulatory mechanism, adenosine (ADO) protects tissues from excessive immune responses, but as a metabolite highly concentrated in tumor microenvironments, extracellular adenosine acts on adenosine receptors (mainly A2A receptors) expressed on MDSCs, Tregs, NK cells, effector T cells, DCs, and macrophages to promote tumor cell escape from immune surveillance by inhibiting the immune response. Amounting preclinical studies have demonstrated the adenosine pathway as a novel checkpoint for immunotherapy. Large number of adenosine pathway targeting clinical trials are now underway, including antibodies against CD39 and CD73 as well as A2A receptor inhibitors. There has been evidence of antitumor efficacy of these inhibitors in early clinical trials among a variety of tumors such as breast cancer, prostate cancer, non-small cell lung cancer, etc. As more clinical trial results are published, the combination of blockade of this pathway with immune checkpoint inhibitors, targeted drugs, traditional chemotherapy medications, radiotherapy and endocrine therapy will provide cancer patients with better clinical outcomes. We would elaborate on the role of CD39-CD73-A2AR pathway in the contribution of tumor microenvironment and the targeting of the adenosinergic pathway for cancer therapy in the review.
Topics: Male; Humans; Adenosine; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immunotherapy; T-Lymphocytes; Tumor Microenvironment
PubMed: 37913941
DOI: 10.1016/j.bbcan.2023.189005