前列腺癌细胞中HEY1基因转录调控分子机制的初步研究
摘要
HEY1是在内皮细胞血管形成中发挥重要作用的转录抑制子,是HEY基因家族成员,该家族成员参与心脏瓣膜形成,心肌及大血管发育,还可通过介导Notch信号系统影响心脏发育。HEY1是一个Notch信号通路的直接靶基因,而Notch信号通路在肿瘤发生发展中具有重要的意义。Notch1信号激活导致前列腺癌细胞的生长抑制。但是,HEY1的机制以及其对前列腺癌细胞影响的研究还未见报道。
我们的实验发现,HEY1与Polycomb group(PcG)蛋白在两种恶性程度不同的前列腺癌细胞系LNCaP和DU145中表达水平明显呈现负相关,并且将PcG蛋白成员EZH2,SUZ12,BMI1干涉后提高了细胞内源HEY1基因mRNA和蛋白表达水平,证实PcG家族蛋白尤其是SUZ12能够调控HEY1基因的转录;RT-PCR,Real time PCR和Western blot结果显示,抗癌药物DNA甲基化酶抑制剂5-aza-dc能够显著提高HEY1基因的mRNA和蛋白表达水平,这也揭示了DNA甲基化可能参与HEY1基因的调控;我们在DU145细胞中过表达HEY1,结果显示,细胞生长停滞在G1期,说明HEY1与细胞周期密切相关。
本项研究初步探讨了HEY1基因转录调控的机制,为深入研究HEY1基因在前列腺癌发生发展中的作用奠定了基础。
HEY1 is an important transcription corepressor in the formation of vascular endothelial cells,and it is a member of HEY gene family which participates in the formation of cardiac valves,development of cardiac muscle and aorta. What is more,it can influence heart development by mediating Notch signaling pathway. HEY1 is the direct target gene of the Notch signal pathway, whereas Notch signaling pathway has a significant role in generation and development of tumor. The activation of Notch1 can result in growth inhibition of prostate cancer cell. However, the transcriptional regulation mechanism and influence on prostate cancer cell of HEY1 gene remain to be discovered.
According to the experiment, we found that the expression of HEY1 had a significant negative correlation in two prostate cancer cells of distinct grade malignancy—LNCaP and DU145. And interference of the PcG protein components EZH2,SUZ12,BMI1 promoted the mRNA and protein level of HEY1 gene, indicating PcG protein, especially SUZ12 can regulate the transcription of HEY1 gene; The result of RT-PCR, Real time PCR and Western blot showed that anti-cancer drug DNA methylase inhibitor 5-aza-dc could remarkably promote the mRNA and protein level of HEY1 gene, indicating that DNA methylation might participate in the regulation of HEY1 gene; We overexpressed HEY1 gene in DU145, and the result showed that the cell growth arrested in the G1 phase, indicating HEY1 gene was closely related to the cell cycle.
The study briefly exploited transcriptional regulation mechanism of HEY1 gene, laying a good foundation to deeply further study the role of HEY1 gene in generation and development in prostate cancer cells.
我们的实验发现,HEY1与Polycomb group(PcG)蛋白在两种恶性程度不同的前列腺癌细胞系LNCaP和DU145中表达水平明显呈现负相关,并且将PcG蛋白成员EZH2,SUZ12,BMI1干涉后提高了细胞内源HEY1基因mRNA和蛋白表达水平,证实PcG家族蛋白尤其是SUZ12能够调控HEY1基因的转录;RT-PCR,Real time PCR和Western blot结果显示,抗癌药物DNA甲基化酶抑制剂5-aza-dc能够显著提高HEY1基因的mRNA和蛋白表达水平,这也揭示了DNA甲基化可能参与HEY1基因的调控;我们在DU145细胞中过表达HEY1,结果显示,细胞生长停滞在G1期,说明HEY1与细胞周期密切相关。
本项研究初步探讨了HEY1基因转录调控的机制,为深入研究HEY1基因在前列腺癌发生发展中的作用奠定了基础。
HEY1 is an important transcription corepressor in the formation of vascular endothelial cells,and it is a member of HEY gene family which participates in the formation of cardiac valves,development of cardiac muscle and aorta. What is more,it can influence heart development by mediating Notch signaling pathway. HEY1 is the direct target gene of the Notch signal pathway, whereas Notch signaling pathway has a significant role in generation and development of tumor. The activation of Notch1 can result in growth inhibition of prostate cancer cell. However, the transcriptional regulation mechanism and influence on prostate cancer cell of HEY1 gene remain to be discovered.
According to the experiment, we found that the expression of HEY1 had a significant negative correlation in two prostate cancer cells of distinct grade malignancy—LNCaP and DU145. And interference of the PcG protein components EZH2,SUZ12,BMI1 promoted the mRNA and protein level of HEY1 gene, indicating PcG protein, especially SUZ12 can regulate the transcription of HEY1 gene; The result of RT-PCR, Real time PCR and Western blot showed that anti-cancer drug DNA methylase inhibitor 5-aza-dc could remarkably promote the mRNA and protein level of HEY1 gene, indicating that DNA methylation might participate in the regulation of HEY1 gene; We overexpressed HEY1 gene in DU145, and the result showed that the cell growth arrested in the G1 phase, indicating HEY1 gene was closely related to the cell cycle.
The study briefly exploited transcriptional regulation mechanism of HEY1 gene, laying a good foundation to deeply further study the role of HEY1 gene in generation and development in prostate cancer cells.
引文
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