目的筛选鼻咽癌紫杉醇化疗抗性细胞死亡相关基因,并探讨筛选出的基因SNCA与FOXC2的相关性。方法通过Cell Death PCR array筛选鼻咽癌化疗敏感细胞(CNE2)和化疗抗性细胞(CNE2/t)之间的差异表达基因。采用Realtime PCR和Western blotting...目的筛选鼻咽癌紫杉醇化疗抗性细胞死亡相关基因,并探讨筛选出的基因SNCA与FOXC2的相关性。方法通过Cell Death PCR array筛选鼻咽癌化疗敏感细胞(CNE2)和化疗抗性细胞(CNE2/t)之间的差异表达基因。采用Realtime PCR和Western blotting检测CNE2和CNE2/t中SNCA的表达差异;采用Real-time PCR检测FOXC2干扰的CNE2/t细胞及其阴性对照细胞中SNCA的表达变化;运用JASPAR数据库预测FOXC2对SNCA的靶向调控作用。结果通过Cell Death PCR array筛选出了CNE2和CNE2/t之间的差异表达基因SNCA。与CNE2细胞相比,CNE2/t细胞中SNCA的mRNA及蛋白表达水平均显著上调(P<0.01)。与阴性对照细胞相比,FOXC2干扰的CNE2/t细胞中SNCA的mRNA表达水平显著下调(P<0.01)。JASPAR数据库预测结果显示,SNCA启动子区中存在FOXC2的结合位点。结论SNCA表达上调与鼻咽癌紫杉醇化疗抗性密切相关,FOXC2可通过调节SNCA促进鼻咽癌的化疗抗性。展开更多
Parkinson＇s disease （PD） is a common neurodegenerative disorder affecting millions of people worldwide, but its cause and pathogenesis are still not fully understood. Earlier studies have shown that SNCA, which enc...Parkinson＇s disease （PD） is a common neurodegenerative disorder affecting millions of people worldwide, but its cause and pathogenesis are still not fully understood. Earlier studies have shown that SNCA, which encodes α-synuclein, is one of the key genes associated with PD. Single-nucleotide polymorphism （SNP） variants of SNCA are thought to be correlated with disease onset. The underlying mechanisms however are enigmatic. A recent study published in Nature revealed that one of the SNP variants in the SNCA non-coding element elevated α- synuclein expression in human neurons by reducing the binding efficiency of transcription factors, demonstrating a previously uncharted role for SNPs in the pathogenesis of PD.展开更多
SNCA,GBA,and VPS35 are three common genes associated with Parkinson's disease.Previous studies have shown that these three genes may be associated with Alzheimer's disease(AD).However,it is unclear whether the...SNCA,GBA,and VPS35 are three common genes associated with Parkinson's disease.Previous studies have shown that these three genes may be associated with Alzheimer's disease(AD).However,it is unclear whether these genes increase the risk of AD in Chinese populations.In this study,we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA,SNCA,and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China.The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population.These findings suggest that the mutations in GBA,SNCA,and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations.The study was approved by the Ethics Committee of Xiangya Hospital,Central South University,China on March 9,2016(approval No.201603198).展开更多
Parkinson’s disease (PD) is one of the most common human neurodegenerative disorders caused by the loss of dopaminergic neurons in the brain. The α-synuclein (SNCA) gene is one of the most studied genes involved in ...Parkinson’s disease (PD) is one of the most common human neurodegenerative disorders caused by the loss of dopaminergic neurons in the brain. The α-synuclein (SNCA) gene is one of the most studied genes involved in the pathogenesis of PD. In our study, we conducted a genetic analysis of promoter and intron single-nucleotide polymorphisms (SNPs) in the SNCA gene. We also analyzed the association of genotypes of these SNPs with expression levels of SNCA mRNA. One of four SNPs in the SNCA gene, and the rs2736990 polymorphism, associates with the risk of the sporadic form of PD in Russian population. The risk of PD was increased almost twofold in carriers of allele C (odds ratios = 1.9, 95% confidence interval: 1.2-2.91, p = 0.003). However, no association was found between any of the genotypes of SNPs tested (rs2583988, rs2619363, rs2619364 and rs2736990) and alterations in SNCA levels. Our findings support the hypothesis that the rs2736990 polymorphism is associated with PD. SNPs rs2583988, rs2619363 and rs2619364 in the promoter region of the SNCA gene themselves do not significantly influence the expression of SNCA. Most likely, SNCA gene expression is a very complex process that is affected by different genetic and epigenetic factors.展开更多
文摘目的筛选鼻咽癌紫杉醇化疗抗性细胞死亡相关基因,并探讨筛选出的基因SNCA与FOXC2的相关性。方法通过Cell Death PCR array筛选鼻咽癌化疗敏感细胞(CNE2)和化疗抗性细胞(CNE2/t)之间的差异表达基因。采用Realtime PCR和Western blotting检测CNE2和CNE2/t中SNCA的表达差异;采用Real-time PCR检测FOXC2干扰的CNE2/t细胞及其阴性对照细胞中SNCA的表达变化;运用JASPAR数据库预测FOXC2对SNCA的靶向调控作用。结果通过Cell Death PCR array筛选出了CNE2和CNE2/t之间的差异表达基因SNCA。与CNE2细胞相比,CNE2/t细胞中SNCA的mRNA及蛋白表达水平均显著上调(P<0.01)。与阴性对照细胞相比,FOXC2干扰的CNE2/t细胞中SNCA的mRNA表达水平显著下调(P<0.01)。JASPAR数据库预测结果显示,SNCA启动子区中存在FOXC2的结合位点。结论SNCA表达上调与鼻咽癌紫杉醇化疗抗性密切相关,FOXC2可通过调节SNCA促进鼻咽癌的化疗抗性。
文摘Parkinson＇s disease （PD） is a common neurodegenerative disorder affecting millions of people worldwide, but its cause and pathogenesis are still not fully understood. Earlier studies have shown that SNCA, which encodes α-synuclein, is one of the key genes associated with PD. Single-nucleotide polymorphism （SNP） variants of SNCA are thought to be correlated with disease onset. The underlying mechanisms however are enigmatic. A recent study published in Nature revealed that one of the SNP variants in the SNCA non-coding element elevated α- synuclein expression in human neurons by reducing the binding efficiency of transcription factors, demonstrating a previously uncharted role for SNPs in the pathogenesis of PD.
基金supported by the National Natural Science Foundation of China,Nos.81971029 (to LS) and 82071216 (to BJ)。
文摘SNCA,GBA,and VPS35 are three common genes associated with Parkinson's disease.Previous studies have shown that these three genes may be associated with Alzheimer's disease(AD).However,it is unclear whether these genes increase the risk of AD in Chinese populations.In this study,we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA,SNCA,and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China.The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population.These findings suggest that the mutations in GBA,SNCA,and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations.The study was approved by the Ethics Committee of Xiangya Hospital,Central South University,China on March 9,2016(approval No.201603198).
文摘Parkinson’s disease (PD) is one of the most common human neurodegenerative disorders caused by the loss of dopaminergic neurons in the brain. The α-synuclein (SNCA) gene is one of the most studied genes involved in the pathogenesis of PD. In our study, we conducted a genetic analysis of promoter and intron single-nucleotide polymorphisms (SNPs) in the SNCA gene. We also analyzed the association of genotypes of these SNPs with expression levels of SNCA mRNA. One of four SNPs in the SNCA gene, and the rs2736990 polymorphism, associates with the risk of the sporadic form of PD in Russian population. The risk of PD was increased almost twofold in carriers of allele C (odds ratios = 1.9, 95% confidence interval: 1.2-2.91, p = 0.003). However, no association was found between any of the genotypes of SNPs tested (rs2583988, rs2619363, rs2619364 and rs2736990) and alterations in SNCA levels. Our findings support the hypothesis that the rs2736990 polymorphism is associated with PD. SNPs rs2583988, rs2619363 and rs2619364 in the promoter region of the SNCA gene themselves do not significantly influence the expression of SNCA. Most likely, SNCA gene expression is a very complex process that is affected by different genetic and epigenetic factors.
