Preliminary Study On The Role Of NCAPG2 In The Progression Of Prostate Cancer And Its Potential Molecular Mechanism

Objective: Prostate cancer(PCa)is the second leading cause of cancer-related mortality among men worldwide,and its incidence has risen substantially in recent years.Therefore,there is an urgent need to identify novel biomarkers and precise therapeutic targets for controlling PCa progression and recurrence.Therefore,we investigated the clinical significance of NCAPG2 in PCa by exploring public datasets and our tissue microarray,containing 150 tissues.Methods:Receiver operating characteristic(ROC)curve and survival analyses were performed to evaluate the correlation between NCAPG2 expression and disease progression.Cell proliferation,wound healing,transwell,cell apoptosis,cell cycle,tumor sphere formation were conducted to further elucidate the molecular mechanism of NCAPG2 in PCa.Subcutaneous and orthotopic xenograft models were used to investigate the effects of NCAPG2 on tumor proliferation in vivo.Tandem mass tag(TMT)quantitative proteomics was employed to detect proteomic changes under NCPAG2 overexpression.Gene Set Enrichment Analysis(GSEA)was used to analyze biological activities associated with NCAPG2 expression.Results:NCAPG2 was significantly upregulated in PCa tissues,and its expression was associated with PCa progression and poor prognosis.In vitro assays indicated that the knockdown of NCAPG2 inhibited the malignant behavior of PCa cells,whereas its overexpression promoted it.NCAPG2 depletion attenuated the development and growth of PCa in vivo.TMT quantitative proteomics and bioinformatics analyses indicated that c-MYC activity was strongly correlated with NCAPG2 expression.The malignancy-promoting effect of NCAPG2 in PCa was mediated via c-MYC.Furthermore,NCAPG2 was positively correlated with PCa cancer stem cell marker expression and could drive PCa stemness.We also observed NCAPG2downregulation-associated decline in the self-renewal ability of PCa cell lines.Conclusion:NCAPG2 expression is upregulated in PCa tissues,and it’s levels are associated with poor PCa prognosis.NCAPG2 promotes PCa malignancy via c-MYC.NCAPG2 drives cancer stemness,highlighting its potential as a therapeutic target.