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目的:探讨前列腺特异性膜抗原(prostate-specific membrane antigen,PSMA)在前列腺癌转移过程中的作用通路。方法:针对PSMA mRNA序列设计合成siRNA序列,脂质体转染LNCaP细胞特异性下调PSMA基因的表达,通过肿瘤转移基因芯片分析84个肿瘤转移相关基因的表达差异。结果:成功设计了siRNA序列并制备最佳干扰效果的干扰样,mRNA干扰效果达到75%以上,蛋白水平干扰效果达68%以上。通过基因芯片检测发现在下调PSMA基因表达后,有CDH6、CXCL12等10个基因发生了显著上调,而CCL7、MDM2等4个基因发生显著下调表达。结论:初步发现PSMA参与前列腺癌转移信号通路的调节,为进一步研究PSMA的生物学功能,探索前列腺癌的转移机制奠定了基础。
Objective: To investigate the role of prostate-specific membrane antigen (PSMA) in the metastasis of prostate cancer. Methods: The siRNA sequences were designed and synthesized based on PSMA mRNA sequence. LNCaP cells transfected with liposome specifically down-regulated the expression of PSMA gene and analyzed the expression differences of 84 metastasis-related genes by tumor metastasis gene chip. RESULTS: siRNA sequences were successfully designed and the interference effect of the siRNA sequence was optimized. The mRNA interference effect reached over 75% and the protein interference effect reached over 68%. The results of gene chip showed that 10 genes such as CDH6 and CXCL12 were significantly upregulated after the down-regulation of PSMA gene expression, while 4 genes such as CCL7 and MDM2 were significantly down-regulated. CONCLUSION: The preliminary findings of PSMA involved in the regulation of metastasis of prostate cancer signal pathway lay the foundation for further study on the biological function of PSMA and exploring the mechanism of metastasis of prostate cancer.