药物成瘾会引起大脑奖赏区域三种主要表观遗传调控的变化,即DNA甲基化,组蛋白修饰和非编码RNA。甲基化CpG结合蛋白2(Methyl-CpG-binding protein 2,MeCP2)是一种调控基因表达的转录抑制因子,在表观遗传机制中发挥重要作用。MeCP2基因突...药物成瘾会引起大脑奖赏区域三种主要表观遗传调控的变化,即DNA甲基化,组蛋白修饰和非编码RNA。甲基化CpG结合蛋白2(Methyl-CpG-binding protein 2,MeCP2)是一种调控基因表达的转录抑制因子,在表观遗传机制中发挥重要作用。MeCP2基因突变引起Rett综合征、孤独症以及其它神经发育障碍性疾病,这已经引起人们对神经元功能中表观遗传修饰重要性的关注。药物成瘾可以诱导行为学和心理学的持续性改变,这些持续性改变由相关神经通路中神经结构的可塑性变化所引起,而MeCP2在调节中枢神经系统突触传递和短时程突触可塑性中起重要作用。本文将讨论MeCP2在中枢神经系统发育和功能中的作用,以及MeCP2参与药物成瘾的潜在重要作用,为药物成瘾的分子机制及临床诊断治疗提供新的思路。展开更多
The aim of this study is to investigate epigenetic mechanism of ABCG2 induced drug-resistance. It is not only expatiate for drug-resistance regulation mechanism in all-round, but also to provide scientific experimenta...The aim of this study is to investigate epigenetic mechanism of ABCG2 induced drug-resistance. It is not only expatiate for drug-resistance regulation mechanism in all-round, but also to provide scientific experimental basis for selecting target to reverse its drug-resistance. Apply methylation-specific PCR （MSP） to have tested methylation of ABCG2 promoter region -359 to -353 specific positions in breast cancer tissues and paired adjacent tissue of 22 cases and test their methylation positions with MSP products for sequencing; and adopt fluorescent quantitation RT-PCR to test expression level DNMT1, DNMT3A, DNMT3B and ABCG2; to make analysis on relationship between them with statistical spearman correlation. Specific positions of ABCG2 gene promoter region of 18 cases among the 22 cases with breast cancer （18/22, 82%） existed high methylation （P〈0.05）, MSP products sequencing proved methylation of the specific position, and mRNA expression level was relative higher in remarkable positive correlation （P〈0.05） ABCG2, DNMT1, DNMT3A, DNMT3B mRNA expression levels in breast cancer tissues were obviously higher than adjacent tissues （P〈0.01）, and DNMT3B expression level was obviously higher than DNMT1 and DNMT3A （P〈0.01） in negative correlation with ABCG2 gene expression （P=0.001）. -359 to -353 positions of promoter regions of ABCG2gene existed high methylation capable to push expression of this gene in beast cancer tissue. DNMT3B is involved in expression regulation in ABCG2 gene, and provides new scientific basis for drug-resistance target as reverse ABCG2 induction展开更多
基金supported by grants from the National Natural Science Foundation of China (No. 81570728)the Natural Science Foundation of Hebei Province,China (No. H2018206358)。
文摘药物成瘾会引起大脑奖赏区域三种主要表观遗传调控的变化,即DNA甲基化,组蛋白修饰和非编码RNA。甲基化CpG结合蛋白2(Methyl-CpG-binding protein 2,MeCP2)是一种调控基因表达的转录抑制因子,在表观遗传机制中发挥重要作用。MeCP2基因突变引起Rett综合征、孤独症以及其它神经发育障碍性疾病,这已经引起人们对神经元功能中表观遗传修饰重要性的关注。药物成瘾可以诱导行为学和心理学的持续性改变,这些持续性改变由相关神经通路中神经结构的可塑性变化所引起,而MeCP2在调节中枢神经系统突触传递和短时程突触可塑性中起重要作用。本文将讨论MeCP2在中枢神经系统发育和功能中的作用,以及MeCP2参与药物成瘾的潜在重要作用,为药物成瘾的分子机制及临床诊断治疗提供新的思路。
基金Supported by the National Natural Science Foundation of China (30500599 and 30571592)the Natural Science Foundation of Guangdong (9151503102000019)the Medical Scientific Research Foundation of Guangdong (A2009606)
文摘The aim of this study is to investigate epigenetic mechanism of ABCG2 induced drug-resistance. It is not only expatiate for drug-resistance regulation mechanism in all-round, but also to provide scientific experimental basis for selecting target to reverse its drug-resistance. Apply methylation-specific PCR （MSP） to have tested methylation of ABCG2 promoter region -359 to -353 specific positions in breast cancer tissues and paired adjacent tissue of 22 cases and test their methylation positions with MSP products for sequencing; and adopt fluorescent quantitation RT-PCR to test expression level DNMT1, DNMT3A, DNMT3B and ABCG2; to make analysis on relationship between them with statistical spearman correlation. Specific positions of ABCG2 gene promoter region of 18 cases among the 22 cases with breast cancer （18/22, 82%） existed high methylation （P〈0.05）, MSP products sequencing proved methylation of the specific position, and mRNA expression level was relative higher in remarkable positive correlation （P〈0.05） ABCG2, DNMT1, DNMT3A, DNMT3B mRNA expression levels in breast cancer tissues were obviously higher than adjacent tissues （P〈0.01）, and DNMT3B expression level was obviously higher than DNMT1 and DNMT3A （P〈0.01） in negative correlation with ABCG2 gene expression （P=0.001）. -359 to -353 positions of promoter regions of ABCG2gene existed high methylation capable to push expression of this gene in beast cancer tissue. DNMT3B is involved in expression regulation in ABCG2 gene, and provides new scientific basis for drug-resistance target as reverse ABCG2 induction
