Transformation Of Methylation Modification Of PIASy And HZimp10 Promoter In Androgen-independent Transition And Cell Apoptosis Of Prostate Cancer

DNA methylation is a usual covalent modification in eukarya genome and is an important part of epigenetics. DNA methylation is one of the modification ways which exist in all kinds of organisms widely. DNA methylation is closely related with tumor growth and proliferation. Change of DNA methylation commonly existed in tumor, which is shown to be highly methylated in cancer suppressor gene and hypomethylated in oncogene. Prostate cancer is the highest incidence of male malignant cancer in the world in which highly methylation of tumor suppressor gene commonly existed, such as STP1,ER and so on. The study on transcription factor promoter methylation is significant for revealing the pathogenesis of malignant tumors.PIASy and hZimp10 are two novel transcriptional regulatory factors. Both of them are selectively expressed in human testis and prostate and have been shown to regulate the transcriptional activity of some suppresser gene, such as P53 and Smad4. However, the transcriptional regulation mechanism and influence on prostate cancer cell of PIASy and hZimp10 remain to be discovered. From the PIASy and hZimp10 promoter methylation of perspective, this study initially revealed their role in the process of Androgen-independent transition and apoptosis.Frist of all, we detected the different evolutional of prostate cancer cells and found the protein expression level of PIASy and hZimp10 are down regulated in the evolution of prostate cancer from an Androgen-dependent state to Androgen-independent state, especially decreased in the Androgen-independent PC3 and DU145 cells, The result suggests that PIASy and hZimp10 may be related to tumor progression. Then we got a result from a software analysis that CpG is extremely rich in the PIASy and hZimp10 promoter sequences, by which can we conclude that methylation modification may be exist in the promoters of PIASy and hZimp10. So we trated DU145 with 5-Azacytidine and detected the methylation modification of the promoter of PIASy and hZimp10 by western blot, the result showed that 5-Azacytidine could remarkably promoted the protein expression level of PIASy while that of hZimp10 are not changed. What's more, we detected the methylation modification of the promoter of PIASy and hZimp10 in three different prostate cancers by MSP. Lower methylation modification of the PIASy promoter was detected in the Androgen-dependent LNCaP cells while that of PIASy promoter was extremely elevated in the Androgen-independent PC3 and DU145 cells.The result indicate that down-regulated expression level of PIASy is caused by the methylation modification of the promoter in the malignant transition process from an Androgen-dependent state to Androgen-independent state. In contrast, the methylation modification of the hZimp10 promoter is inexistent in all of the three prostate cancer cells. Our findings suggest that although the protein expression level is decreased in the process of prostate cancer from an Androgen-dependent state to Androgen-independent state, the molecular mechanism is different.Zinc can induce apoptosis in prostate cancer cells, we analyzed the probable change of the methylation modification in the PIASy promoter during the apoptosis process. We have found that in the apoptosis process induced by Zinc, the protein expression of PIASy and hZimp10 are obviously up-regulated ,but there is no remarkable change of the methylation modification in the PIASy promoter by MSP, which is different from the effect induced by 5-Azacytidine.The above result suggest that the up-regulation of PIASy and hZimp10 induced by Zinc is not related with DNA methylation modification, more intensively research should be given to this molecular mechanism.