The diverse radiation types in medical treatments and the natural environment elicit complex biological effects on both cancerous and non-cancerous tissues.Radiation therapy(RT)induces oncological responses,from molec...The diverse radiation types in medical treatments and the natural environment elicit complex biological effects on both cancerous and non-cancerous tissues.Radiation therapy(RT)induces oncological responses,from molecular to phenotypic alterations,while simultaneously exerting toxic effects on healthy tissue.N^(6)-methyladenosine(m^(6)A),a prevalent modification on coding and non-coding RNAs,is a key epigenetic mark established by a set of evolutionarily conserved enzymes.The interplay between m^(6)A modification and radiobiology of cancerous and non-cancerous tissues merits in-depth investigation.This review summarizes the roles of m^(6)A in the biological effects induced by ionizing radiation and ultraviolet(UV)radiation.It begins with an overview of m^(6)A modification and its detection methods,followed by a detailed examination of how m^(6)A dynamically regulates the sensitivity of cancerous tissues to RT,the injury response in non-cancerous tissues,and the toxicological effects of UV exposure.Notably,this review underscores the importance of novel regulatory mechanisms of m^(6)A and their potential clinical applications in identifying epigenetically modulated radiation-associated biomarkers for cancer therapy and estimation of radiation dosages.In conclusion,enzyme-mediated m^(6)A-modification triggers alterations in target gene expression by affecting the metabolism of the modified RNAs,thus modulating progression and radiosensitivity in cancerous tissues,as well as radiation effects on normal tissues.Several promising avenues for future research are further discussed.This review highlights the importance of m^(6)A modification in the context of radiation biology.Targeting epi-transcriptomic molecules might potentially provide a novel strategy for enhancing the radiosensitivity of cancerous tissues and mitigating radiation-induced injury to normal tissues.展开更多
Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitatio...Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82173467 and 82273577)CAMS Innovation Fund for Medical Sciences(Grant Nos.CIFMS,2022-I2M-2-003 and 2021-I2M-1-042).
文摘The diverse radiation types in medical treatments and the natural environment elicit complex biological effects on both cancerous and non-cancerous tissues.Radiation therapy(RT)induces oncological responses,from molecular to phenotypic alterations,while simultaneously exerting toxic effects on healthy tissue.N^(6)-methyladenosine(m^(6)A),a prevalent modification on coding and non-coding RNAs,is a key epigenetic mark established by a set of evolutionarily conserved enzymes.The interplay between m^(6)A modification and radiobiology of cancerous and non-cancerous tissues merits in-depth investigation.This review summarizes the roles of m^(6)A in the biological effects induced by ionizing radiation and ultraviolet(UV)radiation.It begins with an overview of m^(6)A modification and its detection methods,followed by a detailed examination of how m^(6)A dynamically regulates the sensitivity of cancerous tissues to RT,the injury response in non-cancerous tissues,and the toxicological effects of UV exposure.Notably,this review underscores the importance of novel regulatory mechanisms of m^(6)A and their potential clinical applications in identifying epigenetically modulated radiation-associated biomarkers for cancer therapy and estimation of radiation dosages.In conclusion,enzyme-mediated m^(6)A-modification triggers alterations in target gene expression by affecting the metabolism of the modified RNAs,thus modulating progression and radiosensitivity in cancerous tissues,as well as radiation effects on normal tissues.Several promising avenues for future research are further discussed.This review highlights the importance of m^(6)A modification in the context of radiation biology.Targeting epi-transcriptomic molecules might potentially provide a novel strategy for enhancing the radiosensitivity of cancerous tissues and mitigating radiation-induced injury to normal tissues.
基金supported by the Strategic Priority Research Program(Pilot study)“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(No.XDB39040000)CAMS Innovation Fund for Medical Sciences(Nos.2021-I2M-1-003 and 2021-I2M-1-034)+2 种基金National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-017)Beijing Natural Science Foundation(No.7202158)National Natural Science Foundation of China(No.81971293).
文摘Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.
