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| 1 | Crosstalk between metabolic reprogramming and epigenetics in cancer:updates on mechanisms and therapeutic opportunities显示文摘Reversible,spatial,and temporal regulation of metabolic reprogramming and epigenetic homeostasis are prominent hallmarks of carcinogenesis.Cancer cells reprogram their metabolism to meet the high bioenergetic and biosynthetic demands for vigorous proliferation.Epigenetic dysregulation is a common fea-ture of human cancers,which contributes to tumorigenesis and maintenance of the malignant phenotypes by regulating gene expression.The epigenome is sensitive to metabolic changes.Metabolism produces various metabolites that are substrates,cofactors,or inhibitors of epigenetic enzymes.Alterations in metabolic pathways and fluctuations in intermediate metabolites convey information regarding the intracellular metabolic status into the nucleus by modulating the activity of epigenetic enzymes and thus remodeling the epige-netic landscape,inducing transcriptional responses to heterogeneous metabolic requirements.Cancer metabolism is regulated by epigenetic machinery at both transcriptional and post-transcriptional levels.Epigenetic modifiers,chromatin remodelers and non-coding RNAs are integral contributors to the regulatory networks involved in cancer metabolism,facilitating malignant transformation.However,the significance of the close connection between metabolism and epi-genetics in the context of cancer has not been fully deciphered.Thus,it will be constructive to summarize and update the emerging new evidence support-ing this bidirectional crosstalk and deeply assess how the crosstalk between metabolic reprogramming and epigenetic abnormalities could be exploited to optimize treatment paradigms and establish new therapeutic options.In this review,we summarize the central mechanisms by which epigenetics and metabolism reciprocally modulate each other in cancer and elaborate upon and update the major contributions of the interplays between epigenetic aber-rations and metabolic rewiring to cancer initiation and development.Finally,we highlight the potential therapeutic opportunities for hematological malig-nancies and solid tumors by targeting this epigenetic-metabolic circuit.In summary,we endeavored to depict the current understanding of the coordi-nation between these fundamental abnormalities more comprehensively and provide new perspectives for utilizing metabolic and epigenetic targets for cancer treatment. | Tongxin Ge Xiang Gu Renbing Jia Shengfang Ge Peiwei Chai Ai Zhuang Xianqun Fan | 2022 | Cancer Communications2022，42，11： | 0 |
| 2 | Targeting histone deacetylase suppresses tumor growth through eliciting METTL14-modified m6A RNA methylation in ocular melanoma显示文摘Background Diversified histone deacetylation inhibitors(HDACis)have demonstrated encouraging outcomes in multiple malignancies.N6-methyladenine(m6A)is the most prevalent messenger RNA modification that plays an essential role in the regulation of tumorigenesis.Howbeit,an in-depth understanding of the crosstalk between histone acetylation and m6A RNA modifications remains enigmatic.This study aimed to explore the role of histone acetylation and m6A modifications in the regulation of tumorigenesis of ocular melanoma.Methods Histone modification inhibitor screening was used to explore the effects of HDACis on ocular melanoma cells.Dot blot assay was used to detect the global m6A RNA modification level.Multi-omics assays,including RNA-sequencing,cleavage under targets and tagmentation,single-cell sequencing,methylated RNA immunoprecipitation-sequencing(meRIP-seq),and m6A individual nucleotide resolution cross-linking and immunoprecipitation-sequencing(miCLIP-seq),were performed to reveal the mechanisms of HDACis on methyltransferase-like 14(METTL14)and FAT tumor suppressor homolog 4(FAT4)in ocular melanoma.Quantitative real-time polymerase chain reaction(qPCR),western blotting,and immunofluorescent staining were applied to detect the expression of METTL14 and FAT4 in ocular melanoma cells and tissues.Cell models and orthotopic xenograft models were established to determine the roles of METTL14 and FAT4 in the growth of ocular melanoma.RNA-binding protein immunoprecipitation-qPCR,meRIP-seq,miCLIP-seq,and RNA stability assay were adopted to investigate the mechanism by which m6A levels of FAT4 were affected.Results First,we found that ocular melanoma cells presented vulnerability towards HDACis.HDACis triggered the elevation of m6A RNA modification in ocular melanoma.Further studies revealed that METTL14 served as a downstream candidate for HDACis.METTL14 was silenced by the hypo-histone acetylation status,whereas HDACi restored the normal histone acetylation level of METTL14,thereby inducing its expression.Subsequently,METTL14 served as a tumor suppressor by promoting the expression of FAT4,a tumor suppressor,in a m6A-YTH N6-methyladenosine RNA-binding protein 1-dependent manner.Taken together,we found that HDACi restored the histone acetylation level of METTL14 and subsequently elicited METTL14-mediated m6A modification in tumorigenesis.Conclusions These results demonstrate that HDACis exert anti-cancer effects by orchestrating m6A modification,which unveiling a“histone-RNA crosstalk”of the HDAC/METTL14/FAT4 epigenetic cascade in ocular melanoma. | Ai Zhuang Xiang Gu Tongxin Ge Shaoyun Wang Shengfang Ge Peiwei Chai Renbing Jia Xianqun Fan | 2023 | Cancer Communications2023，43，11： | 0 |
| 3 | Extrachromosomal circular DNA: biogenesis, structure, functions and diseases显示文摘Extrachromosomal circular DNA(eccDNA),ranging in size from tens to millions of base pairs,is independent of conventional chromosomes.Recently,eccDNAs have been considered an unanticipated major source of somatic rearrangements,contributing to genomic remodeling through chimeric circularization and reintegration of circular DNA into the linear genome.In addition,the origin of eccDNA is considered to be associated with essential chromatin-related events,including the formation of super-enhancers and DNA repair machineries.Moreover,our understanding of the properties and functions of eccDNA has continuously and greatly expanded.Emerging investigations demonstrate that eccDNAs serve as multifunctional molecules in various organisms during diversified biological processes,such as epigenetic remodeling,telomere trimming,and the regulation of canonical signaling pathways.Importantly,its special distribution potentiates eccDNA as a measurable biomarker in many diseases,especially cancers.The loss of eccDNA homeostasis facilitates tumor initiation,malignant progression,and heterogeneous evolution in many cancers.An in-depth understanding of eccDNA provides novel insights for precision cancer treatment.In this review,we summarized the discovery history of eccDNA,discussed the biogenesis,characteristics,and functions of eccDNA.Moreover,we emphasized the role of eccDNA during tumor pathogenesis and malignant evolution.Therapeutically,we summarized potential clinical applications that target aberrant eccDNA in multiple diseases. | Ludi Yang Ruobing Jia Tongxin Ge Shengfang Ge Ai Zhuang Peiwei Chai Xianqun Fan | 2022 | Signal Transduction and Targeted Therapy2022，7，11： | 0 |
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