目的探讨核糖体蛋白激酶A6(RSK4)在甲状腺乳头状癌(PTC)中的表达及其与临床病理因素的关系。方法 收集200例PTC(A组)和对应的癌旁组织(B组),40例甲状腺良性结节(C组)及其结节旁组织(D组)新鲜标本,提取相应RNA,并逆转录成cDNA,采用实时...目的探讨核糖体蛋白激酶A6(RSK4)在甲状腺乳头状癌(PTC)中的表达及其与临床病理因素的关系。方法 收集200例PTC(A组)和对应的癌旁组织(B组),40例甲状腺良性结节(C组)及其结节旁组织(D组)新鲜标本,提取相应RNA,并逆转录成cDNA,采用实时荧光定量PCR(RT-qPCR)检测RSK4的表达量,并分析其与PTC患者临床病理因素的关系。结果 A组中RSK4表达量显著低于B组( Z =-9.658, P <0.01)和C组( Z =-5.648, P <0.01),但C组RSK4表达量与D组比较差异无显著性( P >0.05)。肿瘤直径>1 cm的PTC组织中RSK4表达量显著低于≤1 cm组( Z =-3.528, P <0.01),有包膜侵犯的PTC组织中RSK4表达量显著低于无包膜侵犯组( Z =-2.822, P <0.01)。结论 RSK4在PTC组织中低表达,且与肿瘤大小、包膜侵犯相关,可能成为PTC诊断和预后评估的潜在生物标志物。展开更多
Huntington's disease(HD) is caused by abnormal CAG repeat expansion in the 5′-end of the Huntingtin(HTT) gene.In addition to the canonical C-terminal full-length huntingtin(htt) nuclear export signal,a cytoplasmi...Huntington's disease(HD) is caused by abnormal CAG repeat expansion in the 5′-end of the Huntingtin(HTT) gene.In addition to the canonical C-terminal full-length huntingtin(htt) nuclear export signal,a cytoplasmic localization-related domain(CLRD) in the N-terminus of htt has recently been reported.Here,we analyzed this domain by introducing deletion and substitution mutations in a truncated N-terminal htt protein and subsequently monitored htt expression,aggregation and subcellular localization by immunocytochemistry and Western blot analysis.We demonstrated that Htt4-17 was the essential sequence for htt cytoplasmic localization.We also found that the subcellular distribution of htt was altered when Htt1-17 was mutated to contain amino acids of different charges,suggesting a structural requirement of Htt1-17 for the cytoplasmic localization of htt. Deletion of the first three amino acids did not affect its association with mitochondria.We observed that defective cytoplasmic localization resulted in a reduction of total htt aggregates and increased nuclear aggregates,indicating that the subcellular distribution of the protein might influence the aggregation process.These studies provide new insight into the molecular mechanism of htt aggregation in HD.展开更多
文摘目的探讨核糖体蛋白激酶A6(RSK4)在甲状腺乳头状癌(PTC)中的表达及其与临床病理因素的关系。方法 收集200例PTC(A组)和对应的癌旁组织(B组),40例甲状腺良性结节(C组)及其结节旁组织(D组)新鲜标本,提取相应RNA,并逆转录成cDNA,采用实时荧光定量PCR(RT-qPCR)检测RSK4的表达量,并分析其与PTC患者临床病理因素的关系。结果 A组中RSK4表达量显著低于B组( Z =-9.658, P <0.01)和C组( Z =-5.648, P <0.01),但C组RSK4表达量与D组比较差异无显著性( P >0.05)。肿瘤直径>1 cm的PTC组织中RSK4表达量显著低于≤1 cm组( Z =-3.528, P <0.01),有包膜侵犯的PTC组织中RSK4表达量显著低于无包膜侵犯组( Z =-2.822, P <0.01)。结论 RSK4在PTC组织中低表达,且与肿瘤大小、包膜侵犯相关,可能成为PTC诊断和预后评估的潜在生物标志物。
基金supported by the National Natural Science Foundation of China(Grant Nos.30770761 and 30971000)
文摘Huntington's disease(HD) is caused by abnormal CAG repeat expansion in the 5′-end of the Huntingtin(HTT) gene.In addition to the canonical C-terminal full-length huntingtin(htt) nuclear export signal,a cytoplasmic localization-related domain(CLRD) in the N-terminus of htt has recently been reported.Here,we analyzed this domain by introducing deletion and substitution mutations in a truncated N-terminal htt protein and subsequently monitored htt expression,aggregation and subcellular localization by immunocytochemistry and Western blot analysis.We demonstrated that Htt4-17 was the essential sequence for htt cytoplasmic localization.We also found that the subcellular distribution of htt was altered when Htt1-17 was mutated to contain amino acids of different charges,suggesting a structural requirement of Htt1-17 for the cytoplasmic localization of htt. Deletion of the first three amino acids did not affect its association with mitochondria.We observed that defective cytoplasmic localization resulted in a reduction of total htt aggregates and increased nuclear aggregates,indicating that the subcellular distribution of the protein might influence the aggregation process.These studies provide new insight into the molecular mechanism of htt aggregation in HD.
