The Role And Mechanism Of TRIM26 Promoting Prostate Cancer Cell Proliferation

IntroductionProstate cancer(PCa)is one of the malignant tumors that threaten the life and health of middle-aged and elderly men,and it is one of the common cancers in men worldwide.According to the 2018 Global Cancer Statistics Report,the incidence of PCa leads in men cancers in 105 out of 185 countries,and it ranks sixth in China.Although the incidence of PCa in China is still at a relatively low level,it has shown a significant upward trend in recent years.With the aging of the population,changes in diet and lifestyle,the incidence of prostate cancer in my country is not optimistic.Therefore,in the face of the increasing incidence of prostate cancer and the obvious differences in the characteristics of prostate cancer between the East and the West,we explore the key factors affecting the incidence of PCa from the molecular level,and find molecular markers and markers that can effectively predict the prognosis of PCa patients.It is particularly important to explore the signaling pathways that affect the occurrence and development of prostate cancer.TRIM26 is a member of the TRIM family(The tripartite motif,TRIM)of the super large protein family.Its protein structure has the characteristic RBC(RING,B box and Coiled-coil domain)structure of the TRIM family at the N-terminus,and the C-terminus is specific Recognize the PRY-SPRY structure that the substrate protein binds to the substrate protein.TRIM protein family can not only maintain the normal physiological functions of the body,but also participate in the regulation process of a variety of disease pathogenesis,including cell differentiation,proliferation,development,apoptosis,transcription regulation,signal transduction,inflammatory immunity and tumorigenesis.Currently,TRIM26 is mainly found to be involved in the antiviral innate immune response,and its role in carcinogenesis are not well understood.In the present study,we investigated the roles of TRIM26 in PCa cell proliferation and associated mechanisms.This study will provide a potential target for PCa treatment.Methods(1)Western Blot was used to detect the expression level of TRIM26 in prostate cancer cells.(2)The cell migration experiment was used to determine the migration ability of PC3 and WPMY-1 cells.(3)The cell scratch test was used to determine the healing and repairing ability of PC3 and WPMY-1 cells.(4)The colony formation experiment was used to determine the ability of PC3 and WPMY-1 cells to form colonies.(5)Use EdU proliferation experiment to determine the proliferation ability of PC3 and WPMY-1 cells.(6)Use Western Blot to detect the expression level of EMT-related proteins.(7)Use Western Blot to detect the protein expression level of Akt/mTOR signaling pathway.(8)Western Blot was used to detect the migration ability of cells treated with S14161 and the expression levels of proteins related to Akt/mTOR signaling pathway.Results(1)Western Blot analysis found that TRIM26 is highly expressed in prostate cancer cells.(2)Overexpression of TRIM26 promotes the proliferation of prostate cancer cells,and knockdown of TRIM26 inhibits the proliferation of prostate cancer cells.(3)Overexpression of TRIM26 promotes the healing and repairing ability of prostate cancer cells.(4)Overexpression of TRIM26 promotes colony formation of prostate cancer cells,and knockdown of TRIM26 inhibits colony formation of prostate cancer cells.(5)Overexpression of TRIM26 promotes the proliferation of prostate cancer cells,and knockdown of TRIM26 inhibits the proliferation of prostate cancer cells.(6)Overexpression of TRIM26 down-regulates the expression of E-cadherin in prostate cancer cells,and correspondingly promotes the expression of N-cadherin and Vimentin,but after knocking down TRIM26,the expression levels of these proteins change in the opposite direction.These results suggest that TRIM26 may promote epithelial-mesenchymal transition(EMT)of prostate cancer cells.(7)Through Western Blot analysis,it was found that overexpression of TRIM26 increased the phosphorylation activation level of Akt/mTOR protein in prostate cancer cells.Knockdown of TRIM26 decreased the phosphorylation level of Akt/mTOR in prostate cancer cells,suggesting that TRIM26 can activate Akt/mTOR signal path.(8)Through the analysis of Western Blot and cell migration experiments,it is found that the small molecule inhibitor S14161 may inhibit the activation of the Akt/mTOR signaling pathway,thereby inhibiting the migration ability of TRIM26 on prostate cancer cells.Conclusions(1)TRIM26 promotes the migration,proliferation,healing and colony forming ability of prostate cancer cells.(2)TRIM26 promotes epithelial-mesenchymal transition of PCa cells.(3)TRIM26 activates the Akt/mTOR signaling pathway in prostate cells.(4)S14161 can inhibit the migration ability of TRIM26 on prostate cancer cells.