Abstract: Objective The of this study was to investigate the effect of UHRF1 on the proliferation and metastasis of breast cancer MDA-MB-231 cells and its mechanism.Methods The effect of silencing UHRF1 gene on the viability of MDA-MB-231 cells was detected by MTT assay.Colony formation assay was performed to analyze the effect of silencing UHRF1 on cell survival of MDA-MB-231 cells.The effect of silencing UHRF1 on the apoptosis of MDA-MB-231 cells was detected by acridine orange-ethidium bromide (AO / EB).Caspase-3 activity kit was used to detect the expression of caspase-3 in MDA-MB-231 cells.The expressions of Bcl-2,Bax,Bad,p-Bad,XIAP,p53,p21^Cip1/Waf and p16^INK4a were detectedby Western blot.The abilities of invasion and migration of MDA-MB-231 cells silenced by UHRF1were examined by Transwell and Wound healing assays,respectively.Results Silencing UHRF1 significantlydecreased the viability of MDA-MB-231 cells.Silencing UHRF1 decreased colony formation in MDA-MB-231 cells.Depletion of UHRF1 resulted in apoptosis inducedin MDA-MB-231 cells,showing nuclear morphological changes by AO/EB staining and increasing caspase-3 activity.After knockdown of UHRF1,the expression of Bad,XIAP,Bax,p53,p21^Cip1/Waf1 and p16^INK4a was up-regulatedand down-regulated the expression of p-Bad and Bcl-2 in MDA-MB-231 cells.Transwell and wound healing assays demonstrated that silencing UHRF1 could decrease metastasisin MDA-MB-231 cells.Conclusion Silencing UHRF1 can inhibit the viability and survival of MDA-MB-231 cells,and inhibit the invasion and migration of MDA-MB-231 cells regulated by p53/p21^Cip1/Waf1/p16^INK4asignalings.

Key words: UHRF1, Breast cancer, p53, Metastasis, Apoptosis