Multiple endocrine neoplasia type 2A （ MEN2A ） is an autosomal dominant cancer syndrome that is characterized by medullary thyroid carcinoma （MTC）, pheochromaocytoma （50% - 60% of cases ）, and hyperplasia of the...Multiple endocrine neoplasia type 2A （ MEN2A ） is an autosomal dominant cancer syndrome that is characterized by medullary thyroid carcinoma （MTC）, pheochromaocytoma （50% - 60% of cases ）, and hyperplasia of the parathyroid glands （ 20% - 30% of cases ）. MEN-2A comprises a heterogeneous group of neoplastic disorders that most commonly have a single missense substitution of the Ret proto-oncogene （RET） involving exons 10 and 11. Here, we reported a novel case of MEN2A associated with two variations in two distinct genes, Cys634Gly in RET and a rare Ser73Gly substitution in succinate dehydrogenase, subunit D （SDHD）. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma but without parathyroid gland involvement, we speculated that this clinical feature could be correlated with the two substitutions. This is the first report of a MEN2A case involving two different changes one in the RET gene and the other in the SDHD gene.展开更多
Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectom...Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three展开更多
目的探讨成髓细胞瘤转录因子第2亚型(MYB proto-oncogene like 2,MYBL2)基因在子宫内膜癌组织中的表达及拷贝数变异(copy number variation,CNV)情况,评价其与临床特征的关系和对临床预后的影响。方法从癌症基因组图谱(The Cancer Genom...目的探讨成髓细胞瘤转录因子第2亚型(MYB proto-oncogene like 2,MYBL2)基因在子宫内膜癌组织中的表达及拷贝数变异(copy number variation,CNV)情况,评价其与临床特征的关系和对临床预后的影响。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中获取临床病理特征和相应的基因组数据资料完整的子宫内膜癌患者140例,从cBio Cancer Genomics Portal(cBioPortal)数据库下载MYBL2基因CNV和基因组数据资料完整的子宫内膜癌患者137例,以各基因表达水平的中位数作为高低表达的截断值,通过χ2检验和Cox回归分析MYBL2基因高表达及CNV与子宫内膜癌临床特征的关系,Kaplan-Meier曲线分析MYBL2基因表达和CNV与患者预后之间的关系。收集2015年1月至2015年12月南昌大学第二附属医院手术切除经病理组织学确诊的60例子宫内膜癌组织及其癌旁组织。免疫组织化学法检测其MYBL2表达。结果TCGA数据库分析发现,子宫内膜癌MYBL2高表达和低表达患者在病理类型(P=0.034)和组织分级(P<0.01)方面比较,差异均具有统计学意义。cBioPortal数据库分析发现,子宫内膜癌中MYBL2存在CNV(P<0.01),主要变异形式是拷贝数增加,占26.0%。MYBL2 CNV的患者MYBL2 mRNA表达水平上调(P<0.01),MYBL2 CNV患者总生存期与无瘤生存期较短(均P<0.05)。Ⅱ型子宫内膜癌中MYBL2 CNV占比高于Ⅰ型(P<0.01)。结论子宫内膜癌组织中MYBL2呈高表达,且与不良预后相关。MYBL2基因CNV在子宫内膜癌中是一种不良预后因素,其可能成为预测子宫内膜癌临床预后的有效生物标志物。展开更多
目的研究miRNA-195在宫颈癌组织和细胞中的表达,分析其对宫颈癌细胞增殖、迁移的影响和作用机制。方法检测35例临床宫颈癌组织及其对应癌旁正常组织中miRNA-195,通过Kaplan-Meier Plotter数据库分析其与宫颈癌患者预后的关系;采用细胞...目的研究miRNA-195在宫颈癌组织和细胞中的表达,分析其对宫颈癌细胞增殖、迁移的影响和作用机制。方法检测35例临床宫颈癌组织及其对应癌旁正常组织中miRNA-195,通过Kaplan-Meier Plotter数据库分析其与宫颈癌患者预后的关系;采用细胞增殖实验和划痕迁移实验验证miRNA-195对宫颈癌siHa,Hela细胞增殖、迁移的影响;通过microRNA数据库预测miRNA-195的靶基因,双荧光素酶基因实验验证靶向结合关系;qRT-PCR验证miRNA-195对靶基因的调控;分析宫颈癌中靶基因的表达作用及与miRNA-195的相关性,通过细胞回补实验验证miRNA-195是否通过靶向调控蛋白表达在宫颈癌中发挥功能。结果宫颈癌组织中miRNA-195相对表达低于癌旁正常组织(21.03±5.17 vs 40.67±7.92),差异有统计学意义(t=12.285,P<0.001),且具有低表达预后差的临床特征(Logrank P=0.032)。过表达miRNA-195抑制了宫颈癌细胞的增殖(t=6.725~21.433,均P<0.01)和迁移速率(t=12.443,16.749,均P<0.001)。CCND2和MYB是miRNA-195的靶基因,过表达miRNA-195显著抑制了CCND2和MYB mRNA的蛋白表达(P<0.01)。宫颈癌组织中CCND2较癌旁正常组织显著高表达(52.67±4.79 vs 39.86±6.39),差异有统计学意义(t=12.453,P<0.001);MYB较癌旁正常组织显著高表达(43.06±6.43 vs 22.07±6.85),差异有统计学意义(t=13.217,P<0.001);且分别与miRNA-195表达呈负相关(r=-0.726,-0.592,均P<0.05)。过表达CCND2和MYB显著促进了宫颈癌细胞的增殖和迁移速率,敲低CCND2和MYB表达则得到与之相反的结果(F=144.947,875.160,均P<0.001);在过表达miRNA-195细胞中分别回补过表达CCND2和MYB后细胞增殖、迁移速率基本回归到正常水平。结论miRNA-195可通过靶向调控CCND2和MYB表达抑制宫颈癌癌细胞的增殖和迁移,进而参与宫颈癌的发生发展。展开更多
Proanthocyanidins(PAs)are the most broadly distributed secondary metabolites that play important roles in various aspects of plant development and response to biotic and abiotic stresses.In this study,we cloned a R2R3...Proanthocyanidins(PAs)are the most broadly distributed secondary metabolites that play important roles in various aspects of plant development and response to biotic and abiotic stresses.In this study,we cloned a R2R3 MYB gene LoMYB29,which has a full-length coding sequence of 921 bp identified in Larix olgensis.Quantitative real-time reverse transcription polymerase chain reaction analysis indicates that LoMYB29 is expressed under mechanical wounding,high light intensity,and NaCl,PEG6000,Methyl Jasmonate,and abscisic acid treatments.Subcellular localization analysis and yeast twohybrid assay localized LoMYB29 to the nucleus,acting as a transcriptional activator.Staining with 4-dimethylaminocinnamaldehyde showed a darker blue-purple color in LoMYB29-overexpressing Arabidopsis seeds compared to that of wild seeds.LoMYB29-overexpression resulted in a significant increase in leaf PA content.The expression of early flavonoid biosynthesis-related gene CHI and late flavonoid biosynthesis-related genes,including DFR,LDOX,and ANR(PA branch gene),were also activated in transgenic plants overexpressing LoMYB29.The results indicate that LoMYB29 plays a positive role in the regulation of PA biosynthesis by activating the expression of PA biosynthetic genes.展开更多
基金Supported by National Nature Science Foundation of China(30771018)Shanghai Rising-Star Program,China(08QA14057)
文摘Multiple endocrine neoplasia type 2A （ MEN2A ） is an autosomal dominant cancer syndrome that is characterized by medullary thyroid carcinoma （MTC）, pheochromaocytoma （50% - 60% of cases ）, and hyperplasia of the parathyroid glands （ 20% - 30% of cases ）. MEN-2A comprises a heterogeneous group of neoplastic disorders that most commonly have a single missense substitution of the Ret proto-oncogene （RET） involving exons 10 and 11. Here, we reported a novel case of MEN2A associated with two variations in two distinct genes, Cys634Gly in RET and a rare Ser73Gly substitution in succinate dehydrogenase, subunit D （SDHD）. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma but without parathyroid gland involvement, we speculated that this clinical feature could be correlated with the two substitutions. This is the first report of a MEN2A case involving two different changes one in the RET gene and the other in the SDHD gene.
文摘Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three
文摘目的探讨成髓细胞瘤转录因子第2亚型(MYB proto-oncogene like 2,MYBL2)基因在子宫内膜癌组织中的表达及拷贝数变异(copy number variation,CNV)情况,评价其与临床特征的关系和对临床预后的影响。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中获取临床病理特征和相应的基因组数据资料完整的子宫内膜癌患者140例,从cBio Cancer Genomics Portal(cBioPortal)数据库下载MYBL2基因CNV和基因组数据资料完整的子宫内膜癌患者137例,以各基因表达水平的中位数作为高低表达的截断值,通过χ2检验和Cox回归分析MYBL2基因高表达及CNV与子宫内膜癌临床特征的关系,Kaplan-Meier曲线分析MYBL2基因表达和CNV与患者预后之间的关系。收集2015年1月至2015年12月南昌大学第二附属医院手术切除经病理组织学确诊的60例子宫内膜癌组织及其癌旁组织。免疫组织化学法检测其MYBL2表达。结果TCGA数据库分析发现,子宫内膜癌MYBL2高表达和低表达患者在病理类型(P=0.034)和组织分级(P<0.01)方面比较,差异均具有统计学意义。cBioPortal数据库分析发现,子宫内膜癌中MYBL2存在CNV(P<0.01),主要变异形式是拷贝数增加,占26.0%。MYBL2 CNV的患者MYBL2 mRNA表达水平上调(P<0.01),MYBL2 CNV患者总生存期与无瘤生存期较短(均P<0.05)。Ⅱ型子宫内膜癌中MYBL2 CNV占比高于Ⅰ型(P<0.01)。结论子宫内膜癌组织中MYBL2呈高表达,且与不良预后相关。MYBL2基因CNV在子宫内膜癌中是一种不良预后因素,其可能成为预测子宫内膜癌临床预后的有效生物标志物。
文摘目的研究miRNA-195在宫颈癌组织和细胞中的表达,分析其对宫颈癌细胞增殖、迁移的影响和作用机制。方法检测35例临床宫颈癌组织及其对应癌旁正常组织中miRNA-195,通过Kaplan-Meier Plotter数据库分析其与宫颈癌患者预后的关系;采用细胞增殖实验和划痕迁移实验验证miRNA-195对宫颈癌siHa,Hela细胞增殖、迁移的影响;通过microRNA数据库预测miRNA-195的靶基因,双荧光素酶基因实验验证靶向结合关系;qRT-PCR验证miRNA-195对靶基因的调控;分析宫颈癌中靶基因的表达作用及与miRNA-195的相关性,通过细胞回补实验验证miRNA-195是否通过靶向调控蛋白表达在宫颈癌中发挥功能。结果宫颈癌组织中miRNA-195相对表达低于癌旁正常组织(21.03±5.17 vs 40.67±7.92),差异有统计学意义(t=12.285,P<0.001),且具有低表达预后差的临床特征(Logrank P=0.032)。过表达miRNA-195抑制了宫颈癌细胞的增殖(t=6.725~21.433,均P<0.01)和迁移速率(t=12.443,16.749,均P<0.001)。CCND2和MYB是miRNA-195的靶基因,过表达miRNA-195显著抑制了CCND2和MYB mRNA的蛋白表达(P<0.01)。宫颈癌组织中CCND2较癌旁正常组织显著高表达(52.67±4.79 vs 39.86±6.39),差异有统计学意义(t=12.453,P<0.001);MYB较癌旁正常组织显著高表达(43.06±6.43 vs 22.07±6.85),差异有统计学意义(t=13.217,P<0.001);且分别与miRNA-195表达呈负相关(r=-0.726,-0.592,均P<0.05)。过表达CCND2和MYB显著促进了宫颈癌细胞的增殖和迁移速率,敲低CCND2和MYB表达则得到与之相反的结果(F=144.947,875.160,均P<0.001);在过表达miRNA-195细胞中分别回补过表达CCND2和MYB后细胞增殖、迁移速率基本回归到正常水平。结论miRNA-195可通过靶向调控CCND2和MYB表达抑制宫颈癌癌细胞的增殖和迁移,进而参与宫颈癌的发生发展。
基金supported by the Genetically Modified Organisms Breeding Major Projects of China(2018ZX08022001)111 Project(B16010)National High Technology Research and Development Program of China(863 Program,2013AA102704)
文摘Proanthocyanidins(PAs)are the most broadly distributed secondary metabolites that play important roles in various aspects of plant development and response to biotic and abiotic stresses.In this study,we cloned a R2R3 MYB gene LoMYB29,which has a full-length coding sequence of 921 bp identified in Larix olgensis.Quantitative real-time reverse transcription polymerase chain reaction analysis indicates that LoMYB29 is expressed under mechanical wounding,high light intensity,and NaCl,PEG6000,Methyl Jasmonate,and abscisic acid treatments.Subcellular localization analysis and yeast twohybrid assay localized LoMYB29 to the nucleus,acting as a transcriptional activator.Staining with 4-dimethylaminocinnamaldehyde showed a darker blue-purple color in LoMYB29-overexpressing Arabidopsis seeds compared to that of wild seeds.LoMYB29-overexpression resulted in a significant increase in leaf PA content.The expression of early flavonoid biosynthesis-related gene CHI and late flavonoid biosynthesis-related genes,including DFR,LDOX,and ANR(PA branch gene),were also activated in transgenic plants overexpressing LoMYB29.The results indicate that LoMYB29 plays a positive role in the regulation of PA biosynthesis by activating the expression of PA biosynthetic genes.
