The Role Of PARP-1 In Regulation Of Epithelial-Mesenchymal Transition, Proliferation And Migaration In Ovarian Cancer

Part one Expression of PARP-1 in epithelial ovarian cancer tissue and its relationship with epithelial-mesenchymal transitionObjective:To investigate the expression of PARP-1 in epithelial ovarian cancer (EOC) tissue and its relationship with epithelial-mesenchymal transition (EMT).Methods:The expression of PARP-1, E-cadherin, vimentin, Snail was detected in the EOC and benign ovarian tumor tissues by immunohistochemical method, qRT-PCR and western blotting.Results:The positive expression rates of PARP-1, vimentin, Snail were significantly higher in the EOC than that in the benign ovarian tumor tissues, whereas the positive expression rate of E-cadherin was the opposite. The differences were statistically significant (P＜0.05). The expression of PARP-1, E-cadherin, vimentin, Snail in the EOC was associated with the histological grade, clinical stage and lymphatic metastasis (P＜0.05); and no relationship with age and pathological types was observed (P>0.05). The expression of E-cadherin in the EOC was negatively co-related to that of PARP-1; in contrast, the expression of vimentin and Snail in the EOC was positively co-related to that of PARP-1. The relative mRNA, protein expression of PARP-1, vimentin, Snail in the EOC was significantly higher than that in the benign ovarian tumor tissues (P＜0.05), while the mRNA, protein expression of E-cadherin in the EOC was remarkably lower than that in the benign ovarian tumor tissues (P＜0.05).Conclusions:PARP-1 may contribute to the onset of EMT in the EOC by regulating the expression of E-cadherin, vimentin and Snail.The role of PARP-1, which is relevant to EMT, might be important in the development of ovarian cancer.Part two The role of HGF/PARP-1 signaling in regulation of epithelial to mesenchymal transition, proliferation and migration in epithelial ovarian cancerObjective:Investigate the role of Hepatic Growth Factor/Poly ADP-ribose Polymerase-1 (HGF/PARP-1) signaling in regulation of epithelial to mesenchymal transition, proliferation and migration in epithelial ovarian cancer.Methods:Human ovarian cancer cell line SKOV3 was treated with HGF after silencing the PARP-1 gene. Markers of EMT in SKOV3 cells were molecularly assessed by western blotting after the treatments. We also tested the effect of HGF/PARP-1 signaling on ovarian cancer cells by Mossman’s Tetrazole Test (MTT) assay and wound healing assay.Results:HGF could enhance the expression of vimentin and snail. The knockdown of PARP-1 inhibits HGF-stimulated EMT. In the functional experiments, HGF could stimulate the proliferation and migration of SKOV3 cells. Meanwhile, RNA inhibition of PARP-1 attenuates HGF-stimulated SKOV3 cells growth and migration.Conclusions:HGF/PARP-1 promotes tumorigenicity of human ovarian cancer cells in vitro by inducing EMT, enhancing proliferation and migration. Targeting PARP-1 may be an attractive target therapy for ovarian cancer.