The Role And Mechanism Of CircANKS1B In Invasion Of Prostate Cancer And Peptide-modified Gold Nanostar In The Treatment Of Prostate Cancer

Part ?The Role and Mechanism of Circular RNA CircANKSIB in Invision of Prostate CancerBackground:A growing number of studies indicate that circular RNA(circRNA)play critical roles in human diseases,and show great potential as biomarkers and therapeutic targets.This study aimed to investigate the expression and function of circANKS1B in prostate cancer(PCa).Methods:The expression of circANKS IB and miR-152-3p was analyzed by real-time quantitative reverse-transcription polymerase chain reaction(qRT-PCR).Cell migration and invasion were measured using a transwell assay.The interaction between circANKS1B and miR-152-3p was confirmed by a dual-luciferase reporter gene assay.Rescue experiments were conducted to determine whether circANKS1B regulated the invasion of PCa cells via the circANKS1B/miR-152-3p/TGF-? pathway.Results:The expression of circANKS1B was markedly upregulated in both PCa cells and tissues.Moreover,high circANKS1B expression was associated with poor prognosis in PCa patients.Dual-luciferase reporter assay indicated that circANKS1B directly bound to miR-152-3p.Furthermore,circANKS1B negatively regulated miR152-3p expression.Knockdown of circANKS1B markedly suppressed cell migration and invasion and TGF-? expression in PCa cells,whereas the effects of circANKS1B silencing were reversed by miR-152-3p deficiency.In addition,the impact of miR-1523p silencing on invasion of circANKS1B deficient PCa cells was also abrogated by TGF-? deficiency.Overall,circANKSIB acts as a sponge for miR-152-3p to promote PCa progression by upregulating TGF-? expression.Conclusions:Our findings reveal that circANKS1B may be a potential prognostic biomarker and therapeutic target for PCa.Part ?The Role and Mechanism of Peptide-modified Gold Nanostar in the Treatment of Prostate CancerBackground:Blockage of the interaction between programmed death receptor-1(PD-1)and programmed death ligand-1(PD-L1)can restore T-cell activity and enhance antitumor immunity.PD-1/PD-L1 pathway inhibitors have promising applications in the treatment of advanced prostate cancer(PCa).Methods:Using AuNS as the core,the surface of AuNS was modified by PEG and then bound to PD-L1-binding peptide(PD-Llpep)by amide reaction.The uptake of P-AuNS by DU145 cells was observed by confocal laser scanning microscopy(CLSM).The degradation of PD-L1 by P-AuNS was detected by Western blotting(WB),and the transport of P-AuNS in cells was observed by CLSM.The restoration of T cell viability by P-AuNS was examined by the co-culture system of Jurkat cells and DU145 cells,and the antitumor effect of P-AuNS in vivo was studied by the tumor-bearing mouse model of PCa.Results:we successfully developed a peptides-functionalized gold nanoconstruct(P-AuNS-B)consisted of PD-L1-binding peptide(PD-Llpep,P)and gold nanostars(AuNSs),which could bind to cell-surface PD-L1 specifically and deliver PD-L1 into PCa cells with high efficiency.In PCa cells,P-AuNS can efficiently degrade PD-L1 in a lysosomal-dependent manner.In the co-culture system of Jurkat cells and DU145 cells,P-AuNS restored the proliferative capacity and IFN-y secretion level of Jurkat cells inhibited by co-cultured DU145 cells,indicating that P-AuNS effectively hampered the interaction between PD-1 and PD-L1.In addition,in PCa-bearing mice,P-AuNS can effectively inhibit tumor growth and down-regulate PD-L1 protein levels,and in vivo experimental results show that P-AuNS has no systemic toxicity.Conclusions:P-AuNS block the interaction between PD-1 and PD-L1 by efficiently degrading PD-L1,thus restoring the antitumor activity of T cells and inhibiting tumor progression of PCa.P-AuNS has great promise as a potential immunotherapy strategy in the treatment of advanced PCa and even other solid tumors.