The Role Of SETDB1in The Prostate Carcinogenesis

Background：Prostate cancer is one of the most common malignancies, which threathuman being. In developed countries, the incidence rate of prostate cancer takes the firstplace in males and accounts for28%of all cancers. Although lower in China than that inwestern countries, the incidence rate of prostate cancer has been growing. With thedevelopment of PSA screening, the diagnostic rate of prostate cancer has significantlyimproved, while the mortality rate is still high. For early stage prostate cancer, radicalprostatectomy+anti-androgen therapy is effective. However, after a period of time (1-5years) of anti-androgen therapy, nearly all of the prostate cancer cases transform intohormone-refractory prostate cancer (HRPC). The mechanism of HRPC is still unknown,and the lack of effective treatment makes it a leading cause of deaths.SETDB1, which can methylate histone H3K9, is histone methyltransferase. Harte PJet al first discovered and reported it, and confirm that it includes SET domain (Lysinemethyltransferase)1, and that it is located on human chromosome1q21. Researches haveshown that SETDB1gene may promote the growth of Glioma cells. The histonemethyltransferase of melanoma is significantly up regulated that that of normal tissues, andthe up-regulation may promote melanoma. Scholars have used animal models to confirmthis phenomenon and believe SETDB1may intervene the pathogenesis and progression ofmelanoma.Whether SETDB1has similar functions or plays a key role in HRPC is unknown.This research firstly discussed the expression of SETDB1in prostate cancer tissue and therelations to Gleason score and PSA. Then we used siRNA to silence SETDB1andobserved its effect on biological behavior of prostate cancer cells.Objective：To discuss the expression of SETDB1in prostate cancer, its effects onprognosis and the effects on biological behavior of cancer cells.Materials and methods：The expression of SETDB1in80cases of hormone dependentprostate cancer and12cases of hormone independent prostate cancer were compared. Therelationship between different SETDB1expression and Gleason score was observed.SiRNA technique was used to silence SETDB1. The biological behavior of prostate cancercells after silencing SETDB1was observed.Results：1. The expression of SETDB1in80cases of hormone dependent prostate cancer and12cases of hormone independent prostate cancer were compared. Twelve cases ofhormone independent prostate cancer cases were all strongly positive (+++). In80cases ofhormone dependent prostate cancer cases,24of them were weakly positive (+);34werepositive (++);22were strongly positive (+++). The difference was statistically significant(P=0.003).2. SiRNA transfection After interfering the expression of SETDB1, theabilities of proliferation and migration decreased. Silencing SETDB1induces apoptosis ofprostate cancer cells and causes cell cycle arrest at G1/G0. Conclusions SETDB1was upregulated in dependent prostate cancer and hormone independent prostate cancer. It wasrelated to Gleason score. In vitro experiments showed that SETDB1could inhibit thegrowth and proliferation of prostate cancer cells and promote apoptosis.