The Effect of SYT-SSX and Extracellular Signal-Regulated Kinase (ERK) on Cell Proliferation in Synovial Sarcoma
The Effect of SYT-SSX and Extracellular Signal-Regulated Kinase (ERK) on Cell Proliferation in Synovial Sarcoma
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DOI：
10.1007/s12253-010-9334-y
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发表时间：
2011-06-01
影响因子：
2.8
通讯作者：
Sun, Baocun
中科院分区：
文献类型：
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作者：
Cai, Wenjuan;Sun, Yan;Sun, Baocun
滑膜肉瘤的特点是染色体易位t(X；18)(p11.2；q11.2)，导致SYT基因与SSX基因融合。很少有研究能够完全阐明该融合转录本的发病机制。这项研究旨在更深入地了解这种融合基因的功能。我们评估了SYT-SSX的特异性小干扰RNA抑制了SYO-1细胞的全基因组表达。用流式细胞仪和四甲基偶氮唑盐比色法检测细胞增殖和凋亡情况。免疫印迹法检测与细胞增殖相关的蛋白质。对SS组织进行TMA原位末端标记法和免疫组织化学染色。经SYT-SSX特异性siRNA处理后，其mRNA水平下降了90%以上。共有5条通路，其中ERK1/2通路差异显著(p=0.043218)。同时，下调SYT-SSX融合基因的表达会抑制SS细胞的增殖，细胞存活率下降(34.1%)，凋亡率增加(10.92%)。转染SYT-SSX特异性siRNA后，与对照组相比，SYO-1细胞发生G1/G0期阻滞(31.99%)。ERK1/2、p-ERK和细胞周期蛋白D1的蛋白水平与SYT-SSX的表达变化趋势一致。在TMA染色中，高Ki-67LI的SYT-SSX阳性组较SYT-SSX阴性组表达更多的细胞周期蛋白D1和CDK4。在p-ERK表达的病例中检测到高Ki-67LI。同时，在p-ERK表达阳性的肿瘤细胞中，Cyclin D1和CDK4的表达也较高。我们的结果提示，融合基因SYT-SSX可能通过ERK途径在SS细胞生长中发挥重要作用。本研究可能有助于通过所提出的全基因组方法来理解融合基因SYT-SSX在滑膜肉瘤中的致病作用和分子机制。此外，这项研究还将开辟将SYT-SSX和ERK作为治疗靶点的可能性。
The character of Synovial sarcoma is the chromosomal translocation t(X; 18)(p11.2;q11.2), which results in the fusion of the SYT gene with a SSX gene. There is little study that could fully elucidate the mechanism of pathogenesis of this fusion transcript. This study is designed to gain more insight into the function of this fusion gene. We evaluated the whole genome expression in SYO-1 cells inhibited as a result of specific small interfering RNA for SYT-SSX. Cell proliferation and apoptosis were analyzed by flow cytometer and MTT. The proteins correlated with proliferation were also detected using western blot. TUNEL and Immunohistochemical stain assessment were also carried out on TMA of SS tissues. The mRNA level reduced over 90% caused by SYT-SSX specific siRNA. Five pathways were employed, that ERK1/2 pathway was differential significantly (p = 0.043218). Meanwhile, down-regulation of SYT-SSX fusion gene expression would inhibit the proliferation of SS cell and the survival rate decreased (34.1%), while apoptotic rate increased (10.92%). After transfected with SYT-SSX-specific siRNA it caused a block in G1/G0 phase (31.99%) of SYO-1 cells compared with control cells. The protein level of ERK1/2, p-ERK, and cyclin D1 altered in same trend with expression of SYT-SSX. In TMA stain assessment, SYT-SSX positive group with high ki-67 LI expressed more cyclin D1and CDK4 than the SYT-SSX negative group. High ki-67 LI was detected in cases with p-ERK expression. Meanwhile, cyclin D1 and CDK4 were shown to be more expressed in tumor cells with p-ERK expression. Our results suggest that the fusion gene SYT-SSX should be considered to play important role on SS cell growth via ERK pathway. This study may be valuable for understanding the pathogenic role and molecular mechanism of the fusion gene SYT-SSX in synovial sarcoma through the proposed genome-wide approach. Furthermore, the research would open up the possibility of using SYT-SSX and ERK as a therapeutic target.