BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC...BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC.We recommend using these novel markers to assist in clinical decision-making.展开更多
Gene editing has recently emerged as a promising technology to engineer genetic modifications precisely in the genome to achieve long-term relief from corneal disorders.Recent advances in the molecular biology leading...Gene editing has recently emerged as a promising technology to engineer genetic modifications precisely in the genome to achieve long-term relief from corneal disorders.Recent advances in the molecular biology leading to the development of clustered regularly interspaced short palindromic repeats(CRISPRs) and CRISPR-associated systems,zinc finger nucleases and transcription activator like effector nucleases have ushered in a new era for high throughput in vitro and in vivo genome engineering.Genome editing can be successfully used to decipher complex molecular mechanisms underlying disease pathophysiology,develop innovative next generation gene therapy,stem cell-based regenerative therapy,and personalized medicine for corneal and other ocular diseases.In this review we describe latest developments in the field of genome editing,current challenges,and future prospects for the development of personalized genebased medicine for corneal diseases.The gene editing approach is expected to revolutionize current diagnostic and treatment practices for curing blindness.展开更多
目的研究毗邻锌指结构域的溴结构域蛋白2A(bromodomain adjacent to zinc finger domain protein 2,BAZ2A)促进子宫颈癌和肝癌发展的共同机制。方法通过转录组测序获得子宫颈癌组和肝癌组的转录组数据。应用R语言的“limma”包分别筛选...目的研究毗邻锌指结构域的溴结构域蛋白2A(bromodomain adjacent to zinc finger domain protein 2,BAZ2A)促进子宫颈癌和肝癌发展的共同机制。方法通过转录组测序获得子宫颈癌组和肝癌组的转录组数据。应用R语言的“limma”包分别筛选子宫颈癌组DEGs和肝癌组DEGs,并取交集获得其共有DEGs。通过“ggplot2”和“clusterProfiler”包对DEGs进行GO和KEGG功能注释分析。应用STRING数据库在线工具构建子宫颈癌DEGs、肝癌DEGs和共有DEGs的PPI网络分析图。使用Cytoscape软件对PPI网络分析图进行进一步处理,鉴定出核心基因。结果对子宫颈癌DEGs、肝癌DEGs和共有DEGs分别进行KEGG富集,三者共有的通路涉及细胞凋亡、抗原加工与呈递、类固醇生物合成。对子宫颈癌DEGs、肝癌DEGs和共有DEGs分别进行GO富集,前两者共有的生物过程(biological process,BP)条目涉及凋亡信号通路、免疫反应、生物黏附,三者共有的BP条目为细胞-底物黏附。子宫颈癌DEGs的核心基因为EP300。EP300对癌症细胞凋亡、迁移有调控作用。肝癌DEGs的核心基因为HSP90AB1。HSP90AB1可介导细胞程序性死亡、炎症和自身免疫、迁移等过程。共有DEGs的核心基因为RPS3。RPS3是一种核糖体蛋白,可通过影响核糖体的生物发生而影响癌细胞的生长、增殖和转移。结论BAZ2A可通过调节细胞凋亡、免疫反应、细胞运动、迁移而影响子宫颈癌、肝癌的发展,这为癌症的靶向治疗提供了新思路。展开更多
嵌合RNAs是指由两个或两个以上独立基因(即亲本基因)融合产生的新RNAs。传统观点认为,嵌合RNAs都是染色体重排的结果。近年来研究发现,相邻基因间的顺式剪接(cis-splicing of adjacent genes,cis-SAGe)也是产生嵌合RNAs的重要机制之一。...嵌合RNAs是指由两个或两个以上独立基因(即亲本基因)融合产生的新RNAs。传统观点认为,嵌合RNAs都是染色体重排的结果。近年来研究发现,相邻基因间的顺式剪接(cis-splicing of adjacent genes,cis-SAGe)也是产生嵌合RNAs的重要机制之一。cis-SAGe是同一条染色体上位置相邻、转录方向相同的基因间发生转录通读,由此产生的初始转录本经过加工,形成了含有两个或多个亲本基因序列的嵌合RNAs。cis-SAGe最初是在肿瘤细胞中被鉴定出来,其在肿瘤发生中的潜在功能引起了研究者的广泛兴趣。随着研究的深入,人们发现cis-SAGe也广泛存在于正常组织中,可能是哺乳动物进化过程中产生新基因的一种重要机制。本文就cis-SAGe的剪接和表达特性、产生机制及其产物的功能等方面进行了综述,以期为人们全面了解cis-SAGe的研究概况及发展趋势提供参考。展开更多
基金Supported by the Ministry of Science and Technology,Taiwan,No.MOST 104-2314-B-016-010-MY2 and No.MOST 106-2320-B-016-018the Ministry of National Defense,Taiwan,No.MAB-107-075,No.MAB-108-057and No.MAB-109-061
文摘BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC.We recommend using these novel markers to assist in clinical decision-making.
文摘Gene editing has recently emerged as a promising technology to engineer genetic modifications precisely in the genome to achieve long-term relief from corneal disorders.Recent advances in the molecular biology leading to the development of clustered regularly interspaced short palindromic repeats(CRISPRs) and CRISPR-associated systems,zinc finger nucleases and transcription activator like effector nucleases have ushered in a new era for high throughput in vitro and in vivo genome engineering.Genome editing can be successfully used to decipher complex molecular mechanisms underlying disease pathophysiology,develop innovative next generation gene therapy,stem cell-based regenerative therapy,and personalized medicine for corneal and other ocular diseases.In this review we describe latest developments in the field of genome editing,current challenges,and future prospects for the development of personalized genebased medicine for corneal diseases.The gene editing approach is expected to revolutionize current diagnostic and treatment practices for curing blindness.
文摘目的研究毗邻锌指结构域的溴结构域蛋白2A(bromodomain adjacent to zinc finger domain protein 2,BAZ2A)促进子宫颈癌和肝癌发展的共同机制。方法通过转录组测序获得子宫颈癌组和肝癌组的转录组数据。应用R语言的“limma”包分别筛选子宫颈癌组DEGs和肝癌组DEGs,并取交集获得其共有DEGs。通过“ggplot2”和“clusterProfiler”包对DEGs进行GO和KEGG功能注释分析。应用STRING数据库在线工具构建子宫颈癌DEGs、肝癌DEGs和共有DEGs的PPI网络分析图。使用Cytoscape软件对PPI网络分析图进行进一步处理,鉴定出核心基因。结果对子宫颈癌DEGs、肝癌DEGs和共有DEGs分别进行KEGG富集,三者共有的通路涉及细胞凋亡、抗原加工与呈递、类固醇生物合成。对子宫颈癌DEGs、肝癌DEGs和共有DEGs分别进行GO富集,前两者共有的生物过程(biological process,BP)条目涉及凋亡信号通路、免疫反应、生物黏附,三者共有的BP条目为细胞-底物黏附。子宫颈癌DEGs的核心基因为EP300。EP300对癌症细胞凋亡、迁移有调控作用。肝癌DEGs的核心基因为HSP90AB1。HSP90AB1可介导细胞程序性死亡、炎症和自身免疫、迁移等过程。共有DEGs的核心基因为RPS3。RPS3是一种核糖体蛋白,可通过影响核糖体的生物发生而影响癌细胞的生长、增殖和转移。结论BAZ2A可通过调节细胞凋亡、免疫反应、细胞运动、迁移而影响子宫颈癌、肝癌的发展,这为癌症的靶向治疗提供了新思路。
文摘嵌合RNAs是指由两个或两个以上独立基因(即亲本基因)融合产生的新RNAs。传统观点认为,嵌合RNAs都是染色体重排的结果。近年来研究发现,相邻基因间的顺式剪接(cis-splicing of adjacent genes,cis-SAGe)也是产生嵌合RNAs的重要机制之一。cis-SAGe是同一条染色体上位置相邻、转录方向相同的基因间发生转录通读,由此产生的初始转录本经过加工,形成了含有两个或多个亲本基因序列的嵌合RNAs。cis-SAGe最初是在肿瘤细胞中被鉴定出来,其在肿瘤发生中的潜在功能引起了研究者的广泛兴趣。随着研究的深入,人们发现cis-SAGe也广泛存在于正常组织中,可能是哺乳动物进化过程中产生新基因的一种重要机制。本文就cis-SAGe的剪接和表达特性、产生机制及其产物的功能等方面进行了综述,以期为人们全面了解cis-SAGe的研究概况及发展趋势提供参考。
