Role Of BET Inhibitor And Histone Crotonylation In The Cell Of Prostate Cancer

Prostate cancer is a malignant tumor that occurs in the peripheral zone of the prostate in men.Its incidence is increasing year by year,and it has become a malignant disease seriously affecting the health of men.At present,there are many shortcomings in the commonly used clinical treatment methods,and the treatment is in a dilemma.It is urgent to find new treatment directions.We use three BET inhibitors and knocked down BRD4 protein in prostate cancer cell lines LNCaP,C4-2B and PC-3.The effects of BET inhibitors and BRD4 on histone crotonylation modification and related enzymes in prostate cancer were detected by WB and Q-PCR.Sodium crotonate was added to prostate cancer cell lines to detect the effect of histone crotonylation on androgen receptor signaling pathway.The effects of BET inhibitors,BRD4 and crotonylation of histone on the proliferation,migration and invasion of prostate cancer cells were examined by CCK-8,Transwell and scratch tests.After adding inhibitors and knocking down BRD4,the proliferation,migration and invasion of prostate cancer cells were significantly inhibited,androgen receptor signaling pathway was inhibited,the expression of histone acetylase GCN5 and P300 was down-regulated,and the crotonylation modification level of histone decreased.Sodium crotonate can specifically enhance crotonylation modification of histone.When sodium crotonate was added,androgen receptor signaling pathway was activated,and the proliferation,migration and invasion of prostate cancer cells were significantly improved.Therefore,we conclude that BET inhibitors can inhibit androgen receptor signaling pathway and significantly inhibit the proliferation,migration and invasion of prostate cancer cells.Histone crotonylation can activate androgen receptor signaling pathway and promote it...