The Mechanism Of PSMA4 Promoting SOX6 Degradation Through Ubiquitination-proteasome Pathway For The Progression Of Prostate Cancer

ObjectiveProstate cancer is one of the major diseases that endanger the health of men all over the world,and its incidence is increasing year by year.Previous studies in our laboratory found that the abnormal expression of CTBP2 is closely related to the progression of prostate cancer.However,the specific molecular mechanism is still unclear.Relevant research at home and abroad suggests that SOX6 is abnormally expressed in various tumors,but its expression in prostate cancer is also unclear.This article first studies the expression of SOX6 in prostate cancer,and then explores its potential molecular mechanisms affecting the development of prostate cancer.Methods1.Through the analysis of CTBP2 in database,we found that CTBP2 could bind to SOX6,and then speculated whether SOX6 could affect the role of CTBP2 in the development of prostate cancer,which further led to the study of the relationship between SOX6 and prostate cancer.2.The difference of SOX6 expression between clinical prostate cancer patients and benign prostatic hyperplasia patients was detected by immunohistochemistry.Then the SOX6 content in fresh blood samples was detected by ELSIA.The relationship between SOX6 expression and the survival and prognosis of patients with prostate cancer was analyzed with clinical data.3.The abnormal expression of SOX6 in prostate cancer cell lines and normal prostate epithelial cell lines was further verified by RT-qPCR and Western blot.The effects of SOX6 on the biological behavior of prostate cancer cells were confirmed by experiments of cell cloning,cell migration and cell invasion,and the effects of SOX6 on the proliferation of prostate cancer cells were tested in nude mice.4.Finally,we combined the database application bioinformatics technology to explore the potential molecular mechanism of SOX6 affecting the development of prostate cancer.Results1.SOX6 is lowly expressed in prostate cancer and is closely related to the prognosis of patients with prostate cancer.2.SOX6 is also low expressed in prostate cancer cell lines.Knocking down SOX6 can enhance the proliferation and invasion of prostate cancer cell lines.Overexpression of SOX6 can significantly inhibit the biological behavior of prostate cancer cell lines.Nude mice tumorigenesis experiment further confirmed that SOX6 inhibits the proliferation of prostate cancer cells.3.SOX6 can directly combine CTBP2 with CTBP2 to inhibit the proliferation of prostate cancer cells,thereby affecting the role of CTBP2;SOX6 can also inhibit the development of prostate cancer by inhibiting EMT signaling pathway.4.PSMA4,as the upstream of SOX6,can promote SOX6 degradation through ubiquitination-proteasome pathway,leading to prostate cancer progression.ConclusionThe abnormally low expression of SOX6 in prostate cancer is associated with the clinicopathological characteristics of prostate cancer patients,and affects the survival and prognosis of patients.SOX6 is also low expressed in prostate cancer cells,and the abnormal expression of SOX6 affects the biological behavior of prostate cancer cells.Overexpression of SOX6 can significantly inhibit the growth rate of prostate cancer cells.SOX6 can first inhibit the promotion of prostate cancer by directly binding to CTBP2 transcription;secondly,SOX6 can also inhibit the progression of prostate cancer by indirectly inhibiting EMT signaling pathway;then,its upstream factor PSMA4 can cause SOX6 degradation through ubiquitination-proteasome pathway,which ultimately leads to the progression of prostate cancer.