Up-regulation of NKX3.1 Expression and Inhibition of LNCaP Cell Proliferation Induced by an Inhibitory Element Decoy

更新时间:2023-08-14

【摘要】 NKX3.1 is an androgen-regulated prostate-specific homeobox gene that is thought to play animportant role in prostate development and cancerogenesis.NKX3.1 acts as a tumor suppressor gene specificallyin the prostate.Up-regulation of NKX3.1 gene offers a promising gene therapy for prostate cancer.Thedecoy strategy has been developed and is considered a useful tool for regulating gene expression and genetherapy.In our previous studies,we identified a 20 bp inhibitory element upstream of the NKX3.1 promoter.In this study,we focused on using the 20 bp inhibitory element decoy to block negative regulation of theNKX3.1 gene and to up-regulate NKX3.1 expression using synthetic double-stranded oligodeoxynucleotidesof the 20 bp inhibitory element.We found in an electrophoretic mobility shift assay experiment that the 20 bpinhibitory decoy presented competitive binding to a specific binding protein of the 20 bp inhibitory element inprostate cancer cell line LNCaP.In luciferase reporter gene assays,we found that the 20 bp inhibitory decoycould enhance NKX3.1 promoter activity,and RT-PCR and Western blot analysis revealed that NKX3.1expression was up-regulated effectively by the transfection with the 20 bp inhibitory decoy.Furthermore,cell proliferation was inhibited by up-regulated NKX3.1 expression induced by the 20 bp inhibitory decoy.

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