Ribozyme cleavage leads to decreased expression of fibroblast growth factor receptor 3 in human multiple myeloma cells, which is associated with apoptosis and downregulation of vascular endothelial growth factor.
Ribozyme cleavage leads to decreased expression of fibroblast growth factor receptor 3 in human multiple myeloma cells, which is associated with apoptosis and downregulation of vascular endothelial growth factor.
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核酶裂解导致人多发性骨髓瘤细胞中成纤维细胞生长因子受体 3 的表达减少，这与细胞凋亡和血管内皮生长因子的下调有关。
DOI：
10.1089/oli.2005.15.1
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Yen,Yun
中科院分区：
文献类型：
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作者：
Qian,Shenxian;Somlo,George;Zhou,Bingsen;Zhu,Lijun;Mi,Shu;Mo,Xueli;Cheung,EricM;Qiu,Weihua;Lin,Ren-Jang;Rossi,John;Holtz,Melissa;Chu,Peiguo;Yen,Yun
本研究旨在探讨成纤维细胞生长因子受体3（FGFR 3）核酶对多发性骨髓瘤（MM）细胞生长的抑制作用及其机制。我们设计了两个靶向FGFR 3基因的核酶表达质粒Rz 52和Rz 32。在体外，Rz 52和Rz 32在KMS 11细胞中的催化活性使FGFR 3 mRNA表达降低45%。（p< 0.05）和80%（p< 0.5），Rz 52转染的KMS 11克隆的体内检测显示FGFR 3 mRNA表达降低至对照的20%（p< 0.05）。在Rz 52转染的H929克隆中，FGFR 3 mRNA降低至对照的50%。FGFR 3的蛋白质表达降低至亲本KMS 11和H929克隆的70%。转染Rz 52的KMS 11克隆的DNA合成下降到对照的20%，而细胞的存活率下降到对照的2%（p< 0.01）。核酶切割相关的Rz 52 KMS 11转染细胞凋亡的增加是对照的两倍。核酶对FGFR 3表达的抑制与血管内皮生长因子（VEGF）表达的降低和Flt-1的上调有关，但与KDR受体无关。我们的数据表明，FGFR 3是MM细胞的重要细胞存活和抗凋亡因子，并且FGFR 3的核酶靶向下调可能用作以t（4;14）为特征的MM的新型治疗干预。
The aim of this study was to investigate the fibroblast growth factor receptor 3 (FGFR3) mRNA cleavage by ribozymes targeting FGFR3, effect of growth inhibition and associated with mechanism on multiple myeloma (MM). We designated two ribozyme-expressing plasmids that target the FGFR3 genes, Rz52 and Rz32.In vitrocatalytic activity of Rz52 and Rz32 in KMS11 cells decreased FGFR3 mRNA expression to 45% (p< 0.05) and 80% (p< 0.5), respectively, of that of the control.In vivoexamination of the Rz52-transfected KMS11 clone showed that FGFR3 mRNA expression decreased to 20% (p< 0.05) of the control. In the Rz52-transfected H929 clone, FGFR3 mRNA decreased to 50% of the control. Protein expression of FGFR3 decreased to 70% of the parental KMS11 and H929 clones. DNA synthesis in the Rz52-transfected KMS11 clone decreased to 20% of that of the control, whereas the viability of cells decreased to 2% (p< 0.01) of that of the control. Ribozyme cleavage-associated increase in apoptosis of Rz52 KMS11 transfectants was twice that of the control. The inhibition of FGFR3 expression by ribozymes was associated with decreased vascular endothelial growth factor (VEGF) expression and upregulation of Flt-1 but not of the KDR receptor. Our data indicate that FGFR3 is an important cell survival and antiapoptotic factor for MM cells and that ribozyme-targeted downregulation of FGFR3 might be useful as a novel therapeutic intervention in MM characterized by t(4;14).