单胺氧化酶A在维持前列腺癌干性中的作用与机制研究OA

Objective To investigate the role and mechanism of monoamine oxidase A(MAOA)in maintaining the stem cell-like characteristics of prostate cancer to provide an effective target for diagnosis and treatment.Methods The cancer genome atlas database was used for bioinformatics analysis to determine MAOA expression in prostate cancer and its relationship with malignancy degree.Prostate cancer C4-2 cells and patient-derived organoid models were induced with enzalutamide(ENZ)to simulate the clinical pathological process of prostate cancer resistance with enhanced stemness.qRT-PCR was used to detect changes in stemness markers,and Western Blot was used to detect MAOA expression.Lentiviral transfection was used to knock down MAOA,and qRT-PCR and Western Blot were used to detect knockdown efficiency and changes in stemness markers.An ENZ-resistant cell line transplantation model was constructed,and the effect of the MAOA-specific inhibitor clorgyline(CLO)on tumor growth was observed.Lentiviral transfection was used to knock down MAOA;knockdown efficiency and changes in stemness markers were assessed by qRT-PCR and Western Blot to further determine the effect of MAOA on the expression of the stemness-related gene SOX2.Western Blot analysis was also conducted to investigate whether HIF-1α,a key regulator of hypoxia signaling,is involved in MAOA-mediated regulation of SOX2.Additionally,a cell line-derived xenograft(CDX)model was established using enzalutamide-resistant cells,and the effect of the MAOA-specific inhibitor clorgyline(CLO)on tumor growth was evaluated,with qRT-PCR measurement of stemness marker changes.Results MAOA was highly expressed in prostate cancer and was correlated with T stage,N stage,and Gleason score.MAOA expression was enhanced as the degree of stemness increased in the drug-resistant prostate cancer cell model.Conversely,MAOA knockdown significantly reduced tumor cell stemness characteristics and the expression of the stemness-related gene SOX2.Western Blot analysis revealed that hypoxia-inducible factor-1α(HIF-1α),a key regulator of hypoxia signaling,may be involved in the regulation of SOX2 by MAOA.In vivo experiments confirmed that treatment with clorgyline significantly reduced stemness marker expression.Conclusions MAOA upregulated the expression of the cancer stem cell-related gene SOX2 in prostate cancer cells through HIF-1α,enhancing stemness and modulating disease progression.