STAT （Signal Transducers and Activators of Transcription） gene family members have been revealed to be involved in cell growth and differentiation in vertebrates. Despite their physiological importance, their functi...STAT （Signal Transducers and Activators of Transcription） gene family members have been revealed to be involved in cell growth and differentiation in vertebrates. Despite their physiological importance, their functions are poorly studied at organ and systemic levels. In this study, we performed a genome-wide analysis using data from invertebrates to vertebrates to identify STAT genes and analyze their evolutionary history. Interestingly, the STAT gene family undergoes genome duplications during the evolutionary history with STAT3 homologues firstly appearing in the basal extant vertebrate, sea lamprey, suggesting its possible roles in spine formation. To investigate the functions of stat3 in fish species, TALEN technology was performed to generate mutant zebrafish lines, star3 mutant zebrafish showed no obvious defects at early developmental stage but displayed severe lateral and vertical curvature of the spine （scoliosis）, spine fracture and the incomplete bone joints with narrower junction between vertebrae at early juvenile stage, as indicated by Alizarin red and Alcian blue staining, radiography and micro-computed tomography （MicroCT） analysis. Transcriptome analysis reveals dramatic alterations in a number of genes involved in immune and infection response, skeletal development and somatic growth, especially downregulated expression of collagen gene family, in the juvenile stat3 mutant zebrafish. Moreover, most of the collagen genes were detected to have abnormal expression pattern during the formation of spine deformities in stat3 mutants. Our data reveal that stat3 is specially expressed in vertebrates and required for normal spine development and immune function in zebrafish.展开更多
DNA vector-based Stat3-specific RNA interference （si-Stat3） blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on...DNA vector-based Stat3-specific RNA interference （si-Stat3） blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BIJ6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Star3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGFand cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling （TUNEL） assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% （P〈0.01）. Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis （up to 42%, P〈0.01）. The Stat3 downstream genes Bcl-2, VEGFand cyclin DI were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.展开更多
目的:观察STAT3-SURVIVIN途径在槲皮素调控胃癌细胞SGC7901增殖和凋亡中的作用.方法:不同浓度的槲皮素及阳性对照组(AG490 40μmol/L)作用细胞后,MTT法检测细胞毒作用;流式细胞术检测细胞凋亡;Real time RT-PCR,Western Blotting检测sta...目的:观察STAT3-SURVIVIN途径在槲皮素调控胃癌细胞SGC7901增殖和凋亡中的作用.方法:不同浓度的槲皮素及阳性对照组(AG490 40μmol/L)作用细胞后,MTT法检测细胞毒作用;流式细胞术检测细胞凋亡;Real time RT-PCR,Western Blotting检测stat3,survivin基因mRNA及蛋白的表达.结果:随作用时间延长和浓度增高,槲皮素对SGC7901细胞增殖的抑制作用增强.48h槲皮素40μmol/L组与阳性对照组凋亡率相近.Stat3,survivin mRNA之间呈直线相关关系(r=0.697,P=0.002),且p-stat3和survivin蛋白也呈直线相关关系(r=0.748,P=0.003).结论:槲皮素可能通过调控STAT3-SURVIVIN途径抑制胃癌SGC7901细胞增殖并诱导凋亡.展开更多
基金supported by the Fundamental Research Funds for the Central Universities (2662015PY101)the Autonomous Project of State Key Laboratory of Freshwater Ecology and Biotechnology (2011FBZ22)the Autonomous Projects of the Institute of Hydrobiology,Chinese Academy of Sciences (Y25A17, Y45A171301)
文摘STAT （Signal Transducers and Activators of Transcription） gene family members have been revealed to be involved in cell growth and differentiation in vertebrates. Despite their physiological importance, their functions are poorly studied at organ and systemic levels. In this study, we performed a genome-wide analysis using data from invertebrates to vertebrates to identify STAT genes and analyze their evolutionary history. Interestingly, the STAT gene family undergoes genome duplications during the evolutionary history with STAT3 homologues firstly appearing in the basal extant vertebrate, sea lamprey, suggesting its possible roles in spine formation. To investigate the functions of stat3 in fish species, TALEN technology was performed to generate mutant zebrafish lines, star3 mutant zebrafish showed no obvious defects at early developmental stage but displayed severe lateral and vertical curvature of the spine （scoliosis）, spine fracture and the incomplete bone joints with narrower junction between vertebrae at early juvenile stage, as indicated by Alizarin red and Alcian blue staining, radiography and micro-computed tomography （MicroCT） analysis. Transcriptome analysis reveals dramatic alterations in a number of genes involved in immune and infection response, skeletal development and somatic growth, especially downregulated expression of collagen gene family, in the juvenile stat3 mutant zebrafish. Moreover, most of the collagen genes were detected to have abnormal expression pattern during the formation of spine deformities in stat3 mutants. Our data reveal that stat3 is specially expressed in vertebrates and required for normal spine development and immune function in zebrafish.
基金The authors would thank Mr Qiang-Lin Duan for English usage and paper revision.This work was funded by the National Natural Science Foundation of China （No. 30801354, No. 30970791 and No. 30870921）, the Fundamental Research Funds for the Central Universities of China （No. 200810012） and the Jilin Provincial Science ＆ Technology Department, China （No. 20080154）.
文摘DNA vector-based Stat3-specific RNA interference （si-Stat3） blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BIJ6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Star3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGFand cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling （TUNEL） assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% （P〈0.01）. Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis （up to 42%, P〈0.01）. The Stat3 downstream genes Bcl-2, VEGFand cyclin DI were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.
