Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematic...Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematically invest-igates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in tar-geting the retinal microenvironment via a nano-delivery system.Experimental results demonstrate that curcumol activates the demethylase activity of FTO,sta-bilizing the expression of the long non-coding RNA MAFG-AS1,thereby inhi-biting high glucose-induced retinal endothelial cell inflammation,migration,and vascular leakage.Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR:On the one hand,it promotes pathological angiogenesis in endothelial cells,while on the other hand,it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions.Moreover,this study proposes a multidimensional epigenetic regulatory network based on histone lactylation,N6-methyladenosine modification,and DNA methylation,and verifies that curcumol delays DR progression by coordinately modulating these modifications.To overcome the limitations of conventional therapies,this study innovatively designed a macrophage membrane-coated nano-delivery system,significantly enhancing the retinal targeting and bioavailability of curcumol.Finally,the study advocates a paradigm shift from passive treatment to early prevention,proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment.These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.展开更多
In recent years,with the development of medical technology,the detection rate of cancer is getting higher and higher,and the population of patients is getting younger.Many studies have begun to study the early diagnos...In recent years,with the development of medical technology,the detection rate of cancer is getting higher and higher,and the population of patients is getting younger.Many studies have begun to study the early diagnosis,prognostic monitoring markers and pathogenesis of cancer.In recent years,with the development of bioinformatics technology,lncRNA have gradually attracted the attention of researchers.More and more studies have shown that lncRNA are responsible for various biological functions in the process of cancer progression.lncRNA MAFG-AS1 has been shown to be associated with multiple cancers,function as an oncogene,and is significantly associated with poor clinical features and prognosis.This article reviews the research progress of lncRNA MAFG-AS1 in cancer,hoping to provide some help for the future clinical diagnosis and treatment of cancer.展开更多
目的探讨LncRNA-MAFG-AS1在结直肠癌中的表达及临床意义。方法选取我院行手术切除的结直肠癌组织及对应的癌旁正常组织各80例,应用定量即时聚合酶链锁反应(quantitative real time polymerase chain reaction,qRT-PCR)检测结直肠癌组织...目的探讨LncRNA-MAFG-AS1在结直肠癌中的表达及临床意义。方法选取我院行手术切除的结直肠癌组织及对应的癌旁正常组织各80例,应用定量即时聚合酶链锁反应(quantitative real time polymerase chain reaction,qRT-PCR)检测结直肠癌组织及癌旁正常组织中LncRNA-MAFG-AS1的表达水平,并分析其与结直肠癌临床病理特征之间的关系,所有患者随访截止日期到2019年12月31日,应用Kaplan-Meier(K-M)法进行生存分析,采用Cox回归模型分析结直肠癌预后的危险因素。结果结直肠癌组织中LncRNA-MAFG-AS1相对表达量为2.398±0.214,高于癌旁正常组织的1.032±0.132,差异有统计学意义(P<0.05)。当患者TNM分期更高、中高分化及存在淋巴结转移和远期转移时,LncRNA-MAFG-AS1过表达(P<0.05)。K-M生存分析显示高表达患者无进展生存时间(progression-free survival,PFS)为(20.36±3.21)个月,低表达患者为(29.71±4.23)个月;高表达患者的总生存时间(overall survival,OS)为(38.69±6.24)个月,低高表达患者为(54.26±5.14)个月;两组患者的PFS和OS差异有统计学意义(P<0.05)。Cox多因素回归分析显示,TNM分期更高、中高分化及存在淋巴结转移、远期转移以及LncRNA-MAFG-AS1高表达是影响结直肠癌预后的独立危险因素。结论LncRNA-MAFG-AS1在结直肠癌组织中呈高表达,且与结直肠癌患者分化程度、TNM分期、淋巴结和远期转移有关,是影响结直肠癌患者预后的独立风险因素。展开更多
Though promoting ferroptosis can reduce cisplatin resistance in tumor cells,ferroptosis and cisplatin resistance in bladder urothelial carcinoma(BUC)following long non-coding RNAs(lncRNAs)is largely unknown.Here,we fo...Though promoting ferroptosis can reduce cisplatin resistance in tumor cells,ferroptosis and cisplatin resistance in bladder urothelial carcinoma(BUC)following long non-coding RNAs(lncRNAs)is largely unknown.Here,we found the highly expressed lncRNA MAF transcription factor G antisense RNA 1(MAFG-AS1)in BUC,and its inhibition increased the sensitivity of BUC cells to cisplatin by promoting ferroptosis.Mechanically,binding to iron chaperone poly(rC)-binding protein 2(PCBP2)facilitated the recruitments of MAFG-AS1 to deubiquitinase ubiquitin carboxyl-terminal hydrolase isozyme L5(UCHL5),thus stabilizing PCBP2 protein itself.Then PCBP2 was confirmed to interact with ferroportin 1(FPN1),an iron export protein,leading to inhibition of ferroptosis.Moreover,the expression of MAFG-AS1 was regulated by the transcriptional factor MAFG.Interestingly,MAFG-AS1 stimulated MAFG transcription by recruiting histone acetyltransferase p300(EP300)to promote the histone 3 at lysine 27(H3K27ac)at genomic locus of MAFG,forming a MAFG-AS1/MAFG positive feedback loop.In patient samples,higher expression of MAFG-AS1 and MAFG in BUC tissues was significantly correlated with T status and N status,such that MAFG-AS1,MAFG,and the combination of the two were independent prognostic indicators and chemotherapy sensitivity predictive biomarkers for BUC patients.These findings suggest that inhibition of MAFG-AS1 and MAFG can increase the sensitivity of BUC cells to cisplatin through promoting ferroptosis,indicating the novel chemotherapy sensitivity biomarkers and therapeutic target for BUC.展开更多
基金Supported by Quzhou Science and Technology Plan Project,No.2024K076.
文摘Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematically invest-igates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in tar-geting the retinal microenvironment via a nano-delivery system.Experimental results demonstrate that curcumol activates the demethylase activity of FTO,sta-bilizing the expression of the long non-coding RNA MAFG-AS1,thereby inhi-biting high glucose-induced retinal endothelial cell inflammation,migration,and vascular leakage.Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR:On the one hand,it promotes pathological angiogenesis in endothelial cells,while on the other hand,it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions.Moreover,this study proposes a multidimensional epigenetic regulatory network based on histone lactylation,N6-methyladenosine modification,and DNA methylation,and verifies that curcumol delays DR progression by coordinately modulating these modifications.To overcome the limitations of conventional therapies,this study innovatively designed a macrophage membrane-coated nano-delivery system,significantly enhancing the retinal targeting and bioavailability of curcumol.Finally,the study advocates a paradigm shift from passive treatment to early prevention,proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment.These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.
基金Hainan Province Higher Education Science Research Project(No.Hnky2020ZD-15)。
文摘In recent years,with the development of medical technology,the detection rate of cancer is getting higher and higher,and the population of patients is getting younger.Many studies have begun to study the early diagnosis,prognostic monitoring markers and pathogenesis of cancer.In recent years,with the development of bioinformatics technology,lncRNA have gradually attracted the attention of researchers.More and more studies have shown that lncRNA are responsible for various biological functions in the process of cancer progression.lncRNA MAFG-AS1 has been shown to be associated with multiple cancers,function as an oncogene,and is significantly associated with poor clinical features and prognosis.This article reviews the research progress of lncRNA MAFG-AS1 in cancer,hoping to provide some help for the future clinical diagnosis and treatment of cancer.
文摘目的探讨LncRNA-MAFG-AS1在结直肠癌中的表达及临床意义。方法选取我院行手术切除的结直肠癌组织及对应的癌旁正常组织各80例,应用定量即时聚合酶链锁反应(quantitative real time polymerase chain reaction,qRT-PCR)检测结直肠癌组织及癌旁正常组织中LncRNA-MAFG-AS1的表达水平,并分析其与结直肠癌临床病理特征之间的关系,所有患者随访截止日期到2019年12月31日,应用Kaplan-Meier(K-M)法进行生存分析,采用Cox回归模型分析结直肠癌预后的危险因素。结果结直肠癌组织中LncRNA-MAFG-AS1相对表达量为2.398±0.214,高于癌旁正常组织的1.032±0.132,差异有统计学意义(P<0.05)。当患者TNM分期更高、中高分化及存在淋巴结转移和远期转移时,LncRNA-MAFG-AS1过表达(P<0.05)。K-M生存分析显示高表达患者无进展生存时间(progression-free survival,PFS)为(20.36±3.21)个月,低表达患者为(29.71±4.23)个月;高表达患者的总生存时间(overall survival,OS)为(38.69±6.24)个月,低高表达患者为(54.26±5.14)个月;两组患者的PFS和OS差异有统计学意义(P<0.05)。Cox多因素回归分析显示,TNM分期更高、中高分化及存在淋巴结转移、远期转移以及LncRNA-MAFG-AS1高表达是影响结直肠癌预后的独立危险因素。结论LncRNA-MAFG-AS1在结直肠癌组织中呈高表达,且与结直肠癌患者分化程度、TNM分期、淋巴结和远期转移有关,是影响结直肠癌患者预后的独立风险因素。
基金This work was supported by the National Natural Science Foundation of China(81874137)the Outstanding Youth Foundation of Hunan Province(2018JJ1047)+4 种基金the Huxiang Young Talent Project(2016RS3022)the Hunan Province Science and Technology Talent Promotion Project(2019TJ-Q10)the Project of Scientific Research Plan of Health and Family Planning Commission of Hunan Province(c20180476)the Fundamental Research Funds for the Central South University(2018zzts938)the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hosipital of Central South University(ZC060001 and YX202007).
文摘Though promoting ferroptosis can reduce cisplatin resistance in tumor cells,ferroptosis and cisplatin resistance in bladder urothelial carcinoma(BUC)following long non-coding RNAs(lncRNAs)is largely unknown.Here,we found the highly expressed lncRNA MAF transcription factor G antisense RNA 1(MAFG-AS1)in BUC,and its inhibition increased the sensitivity of BUC cells to cisplatin by promoting ferroptosis.Mechanically,binding to iron chaperone poly(rC)-binding protein 2(PCBP2)facilitated the recruitments of MAFG-AS1 to deubiquitinase ubiquitin carboxyl-terminal hydrolase isozyme L5(UCHL5),thus stabilizing PCBP2 protein itself.Then PCBP2 was confirmed to interact with ferroportin 1(FPN1),an iron export protein,leading to inhibition of ferroptosis.Moreover,the expression of MAFG-AS1 was regulated by the transcriptional factor MAFG.Interestingly,MAFG-AS1 stimulated MAFG transcription by recruiting histone acetyltransferase p300(EP300)to promote the histone 3 at lysine 27(H3K27ac)at genomic locus of MAFG,forming a MAFG-AS1/MAFG positive feedback loop.In patient samples,higher expression of MAFG-AS1 and MAFG in BUC tissues was significantly correlated with T status and N status,such that MAFG-AS1,MAFG,and the combination of the two were independent prognostic indicators and chemotherapy sensitivity predictive biomarkers for BUC patients.These findings suggest that inhibition of MAFG-AS1 and MAFG can increase the sensitivity of BUC cells to cisplatin through promoting ferroptosis,indicating the novel chemotherapy sensitivity biomarkers and therapeutic target for BUC.
