MAX Interacts With The AR To Drive Transcriptional Repression In Prostate Cancer

ObjectiveTo determine whether the transcription factor MAX participates in AR-mediated gene transcriptional suppression in prostate cancer cells.The detailed mechanism of MAX's participation in negative AR regulation was detected.Furthermore,it was verified the role of MAX's played during the process from ADPC to CRPC.MethodAfter bioinformatics analysis of the characteristics and commonality of the promoter region of AR negative regulatory genes,MAX was verified to participate in the negative regulation of AR downstream genes by RNA interference and q PCR Then,CO-IP,immunofluorescence,DUO-LINK and other methods were used to verify whether MAX was combined with AR.Subsequently,the genes expression of LNCa P cell line with low MAX expression after DHT stimulation by transcriptome sequencing was established by transcriptome sequencing.Furthermore,Experiments such as Ch IP was carried out to clarify MAX's co-repression role in AR downstream gene.Through drug and regulation of expression of MAX,the mechanism of MAX and AR jointly regulate downstream genes in prostate cancer cells was excavated with q PCR,Western blot,etc.Finally,the effects of MAX on the proliferation and invasion of prostate cancer cells were determined MTT,Invasion Assay and in vivo assayResults1.AR does not inhibit downstream genes transcription via binding specific negative androgen corresponding elements,but can inhibit the transcription of downstream genes by combining with other cofactors such as MAX;2.MAX participates in AR's suppression of downstream gene transcription,and changing MAX expression can reverse transcriptional of negative AR downstream genes in LNCa P cells;3.MAX can interact with AR to repress transcription of AR downstream genes such as NCOR2,MDK.4.Further research found that MAX can combine with AR to promote the deacetylation of H3K56 ac for inhibiting the downstream gene transcription,and deacetylase inhibitor S4 P can reverse this process.5.MAX can inhibit the proliferation and invasion of prostate cancer cells.With the development of prostate cancer,the expression of MAX in tissues gradually decreases.Overexpression of MAX in LNCa P-AI cells can inhibit cell proliferation and invasion in vivo.ConclusionAR can negatively regulate downstream genes by interacting with the cofactor MAX.In the absence of DHT,the expression of downstream genes will increase due to the lack of negative transcriptional regulation of AR and MAX,thereby promoting the proliferation and metastasis of prostate cancer cells.It indicated that the negative regulation of AR has played an important role in the development of prostate cancer from ADPC to CRPC.Further research about the negative regulation of AR can provide new clues and options for the clinical treatment of prostate cancer.