目的探究NPRL2、Survivin在肝细胞肝癌中的作用,两者间的关系及其与各临床指标间的联系。方法收集45例肝细胞肝癌患者的癌组织、癌旁组织及15例正常肝脏组织,采用免疫组织化学方法、实时荧光定量RT-PCR法检测NPRL2、Survivin在各组织中...目的探究NPRL2、Survivin在肝细胞肝癌中的作用,两者间的关系及其与各临床指标间的联系。方法收集45例肝细胞肝癌患者的癌组织、癌旁组织及15例正常肝脏组织,采用免疫组织化学方法、实时荧光定量RT-PCR法检测NPRL2、Survivin在各组织中的表达。结果 NPRL2在肝癌组织中的表达低于其癌旁组织、正常肝脏组织(P<0.01),与肿瘤TNM分期有关(P<0.05)。Survivin在肝癌组织中的表达高于癌旁组织、正常肝脏组织(P<0.01),且与血清AFP浓度、TNM分期有关(P<0.05)。在正常肝脏组织和癌旁组织中,NPRL2、Survivin的表达差异无统计学意义(P>0.05)。Spearman等级相关分析结果表明,NPRL2、Survivin m RNA在肝癌组织中的表达呈负相关(r=-0.45,P<0.01)。结论在肝细胞肝癌中,NPRL2是肿瘤抑制基因,Survivin是癌基因,且两者表达呈负相关,共同参与了肿瘤的发生发展。展开更多
Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study,three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dup ...Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study,three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dup C and 6,706-bp genomic DNA(g DNA) deletion, were identified in three families with focal epilepsy by linkage analysis, whole exome sequencing(WES) and Sanger sequencing. NPRL3 protein is a component of the GATOR1 complex, a major inhibitor of m TOR signaling. These mutations led to truncation of the NPRL3 protein and hampered the binding between NPRL3 and DEPDC5, which is another component of the GATOR1 complex. Consequently, the mutant proteins enhanced m TOR signaling in cultured cells, possibly due to impaired inhibition of m TORC1 by GATOR1. Knockdown of nprl3 in Drosophila resulted in epilepsy-like behavior and abnormal synaptic development. Taken together, these findings expand the genotypic spectrum of NPRL3-associated focal epilepsy and provide further insight into how NPRL3 mutations lead to epilepsy.展开更多
文摘目的探究NPRL2、Survivin在肝细胞肝癌中的作用,两者间的关系及其与各临床指标间的联系。方法收集45例肝细胞肝癌患者的癌组织、癌旁组织及15例正常肝脏组织,采用免疫组织化学方法、实时荧光定量RT-PCR法检测NPRL2、Survivin在各组织中的表达。结果 NPRL2在肝癌组织中的表达低于其癌旁组织、正常肝脏组织(P<0.01),与肿瘤TNM分期有关(P<0.05)。Survivin在肝癌组织中的表达高于癌旁组织、正常肝脏组织(P<0.01),且与血清AFP浓度、TNM分期有关(P<0.05)。在正常肝脏组织和癌旁组织中,NPRL2、Survivin的表达差异无统计学意义(P>0.05)。Spearman等级相关分析结果表明,NPRL2、Survivin m RNA在肝癌组织中的表达呈负相关(r=-0.45,P<0.01)。结论在肝细胞肝癌中,NPRL2是肿瘤抑制基因,Survivin是癌基因,且两者表达呈负相关,共同参与了肿瘤的发生发展。
基金supported by the National Natural Science Foundation of China (32270663, 31871262, U20A20355,32022035)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Ministry of Science and Technology of China STI2030-Major Projects (2021ZD0203202)。
文摘Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study,three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dup C and 6,706-bp genomic DNA(g DNA) deletion, were identified in three families with focal epilepsy by linkage analysis, whole exome sequencing(WES) and Sanger sequencing. NPRL3 protein is a component of the GATOR1 complex, a major inhibitor of m TOR signaling. These mutations led to truncation of the NPRL3 protein and hampered the binding between NPRL3 and DEPDC5, which is another component of the GATOR1 complex. Consequently, the mutant proteins enhanced m TOR signaling in cultured cells, possibly due to impaired inhibition of m TORC1 by GATOR1. Knockdown of nprl3 in Drosophila resulted in epilepsy-like behavior and abnormal synaptic development. Taken together, these findings expand the genotypic spectrum of NPRL3-associated focal epilepsy and provide further insight into how NPRL3 mutations lead to epilepsy.
