目的探讨敲低YTH结构域N^6甲基腺嘌呤(m^6A)RNA结合蛋白2(YTHDF2)对人宫颈癌细胞增殖、周期和凋亡的影响。方法利用人蛋白图谱(Human Protein Atlas)数据库分析YTHDF2在宫颈癌中表达及与生存时间的关系。收集宫颈癌和正常宫颈组织各31例...目的探讨敲低YTH结构域N^6甲基腺嘌呤(m^6A)RNA结合蛋白2(YTHDF2)对人宫颈癌细胞增殖、周期和凋亡的影响。方法利用人蛋白图谱(Human Protein Atlas)数据库分析YTHDF2在宫颈癌中表达及与生存时间的关系。收集宫颈癌和正常宫颈组织各31例,采用免疫组织化学法检测YTHDF2的蛋白表达差异;利用敲低YTHDF2的短发夹RNA(shRNA)及空载质粒包装慢病毒,并感染至宫颈癌HeLa细胞和SiHa细胞,实时荧光定量PCR及Western blot法检测YTHDF2的mRNA及蛋白水平,敲低YTHDF2后,采用CCK-8法检测细胞增殖活性,集落形成实验检测细胞集落形成能力;流式细胞术检测细胞周期和细胞凋亡情况。结果检测数据库发现YTHDF2在宫颈癌中表达越高生存时间越短,与正常宫颈组织相比,YTHDF2在宫颈癌组织高表达。敲低YTHDF2后,抑制宫颈癌细胞增殖,促进细胞凋亡,使细胞阻滞于S期。结论YTHDF2在宫颈癌组织中高表达,敲低后抑制宫颈癌细胞增殖并促进其凋亡。展开更多
As the most prevalent and abundant transcriptional modification in the eukaryotic genome,the continuous and dynamic regulation of N^6-methyladenosine(m^6 A)has been shown to play a vital role in physiological and path...As the most prevalent and abundant transcriptional modification in the eukaryotic genome,the continuous and dynamic regulation of N^6-methyladenosine(m^6 A)has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases(CVDs),such as ischemic heart failure(HF),myocardial hypertrophy,myocardial infarction(MI),and cardiomyogenesis.Regulation is achieved by modulating the expression of m^6 A enzymes and their downstream cardiac genes.In addition,this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs.However,the exact molecular mechanism of m^6 A epigenetic regulation has not been fully elucidated.In this review,we outline recent advances and discuss potential therapeutic strategies for managing m^6 A in relation to several common CVD-related metabolic disorders and external environmental factors.Note that an appropriate understanding of the biological function of m^6 A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms.Finally,it can provide new insights for the development of novel therapeutic agents for use in clinical practice.展开更多
An efficient protocol for the synthesis of N^6-(2-Hydroxyethyl)adenosine and its analogues through nucleophilic substitution was developed. All the reactions were completed in 10 rain under microwave irradiation. Us...An efficient protocol for the synthesis of N^6-(2-Hydroxyethyl)adenosine and its analogues through nucleophilic substitution was developed. All the reactions were completed in 10 rain under microwave irradiation. Using water as solvent makes our method eco-friendly and easy to handle with.展开更多
RNA modifications are abundant in eukaryotes, bacteria, and archaea. N^6-methyladenosine(m^6A), a type of RNA modification mainly found in messenger RNA(mRNA), has significant effects on the metabolism and function of...RNA modifications are abundant in eukaryotes, bacteria, and archaea. N^6-methyladenosine(m^6A), a type of RNA modification mainly found in messenger RNA(mRNA), has significant effects on the metabolism and function of m RNAs. This modification is governed by three types of proteins, namely methyltransferases as ‘‘writers' ', demethylases as ‘‘erasers' ',and specific m^6A-binding proteins(YTHDF1-3) as ‘‘readers' '. Further, it is important for the regulation of cell fate and has a critical function in many biological processes including virus replication, stem cell differentiation, and cancer development, and exerts its effect by controlling gene expression. Herein, we summarize recent advances in research on m^6A in virus replication and T cell regulation, which is a rapidly emerging field that will facilitate the development of antiviral therapies and the study of innate immunity.展开更多
文摘目的探讨敲低YTH结构域N^6甲基腺嘌呤(m^6A)RNA结合蛋白2(YTHDF2)对人宫颈癌细胞增殖、周期和凋亡的影响。方法利用人蛋白图谱(Human Protein Atlas)数据库分析YTHDF2在宫颈癌中表达及与生存时间的关系。收集宫颈癌和正常宫颈组织各31例,采用免疫组织化学法检测YTHDF2的蛋白表达差异;利用敲低YTHDF2的短发夹RNA(shRNA)及空载质粒包装慢病毒,并感染至宫颈癌HeLa细胞和SiHa细胞,实时荧光定量PCR及Western blot法检测YTHDF2的mRNA及蛋白水平,敲低YTHDF2后,采用CCK-8法检测细胞增殖活性,集落形成实验检测细胞集落形成能力;流式细胞术检测细胞周期和细胞凋亡情况。结果检测数据库发现YTHDF2在宫颈癌中表达越高生存时间越短,与正常宫颈组织相比,YTHDF2在宫颈癌组织高表达。敲低YTHDF2后,抑制宫颈癌细胞增殖,促进细胞凋亡,使细胞阻滞于S期。结论YTHDF2在宫颈癌组织中高表达,敲低后抑制宫颈癌细胞增殖并促进其凋亡。
基金Project supported by the Grants-in-Aid from the Graduate Research and Innovation Projects of Jiangsu Province(No.KYCX18_1461),China。
文摘As the most prevalent and abundant transcriptional modification in the eukaryotic genome,the continuous and dynamic regulation of N^6-methyladenosine(m^6 A)has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases(CVDs),such as ischemic heart failure(HF),myocardial hypertrophy,myocardial infarction(MI),and cardiomyogenesis.Regulation is achieved by modulating the expression of m^6 A enzymes and their downstream cardiac genes.In addition,this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs.However,the exact molecular mechanism of m^6 A epigenetic regulation has not been fully elucidated.In this review,we outline recent advances and discuss potential therapeutic strategies for managing m^6 A in relation to several common CVD-related metabolic disorders and external environmental factors.Note that an appropriate understanding of the biological function of m^6 A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms.Finally,it can provide new insights for the development of novel therapeutic agents for use in clinical practice.
基金the National Natural Science Foundation of China(No.20372018)
文摘An efficient protocol for the synthesis of N^6-(2-Hydroxyethyl)adenosine and its analogues through nucleophilic substitution was developed. All the reactions were completed in 10 rain under microwave irradiation. Using water as solvent makes our method eco-friendly and easy to handle with.
基金supported by funding from the National Natural Science Foundation of China (Nos. 81672004, 31270202,81801993, and 81801994)the Jilin University Science and Technology Innovative Research Team (JLUSTIRT, 2017TD-05)+3 种基金the Science and Technology Department of Jilin Province (20160101044JC)the Health and Family Planning Commission of Jilin Province (2013Z066)the Key Laboratory of Molecular Virology, Jilin Province (20102209)China Postdocotoral Science Foundation (2018M631869)
文摘RNA modifications are abundant in eukaryotes, bacteria, and archaea. N^6-methyladenosine(m^6A), a type of RNA modification mainly found in messenger RNA(mRNA), has significant effects on the metabolism and function of m RNAs. This modification is governed by three types of proteins, namely methyltransferases as ‘‘writers' ', demethylases as ‘‘erasers' ',and specific m^6A-binding proteins(YTHDF1-3) as ‘‘readers' '. Further, it is important for the regulation of cell fate and has a critical function in many biological processes including virus replication, stem cell differentiation, and cancer development, and exerts its effect by controlling gene expression. Herein, we summarize recent advances in research on m^6A in virus replication and T cell regulation, which is a rapidly emerging field that will facilitate the development of antiviral therapies and the study of innate immunity.