TiPARP Promotes Epithelial-to-mesenchymal Transition And Metastasis Of Ovarian Cancer

Objective: Ovarian cancer is one of the three most common malignant tumors in the female reproductive system,with the highest mortality rate.The metastasis and recurrence of ovarian cancer are the main reasons for the failure treatment.Ti PAR,a member of the DNA repair enzyme family,is a polyadenosine diphosphate ribose polymerase induced by TCCD.It is a DNA repair enzyme that participates in various regulatory processes such as cell growth and differentiation,damage repair,and energy metabolism.Ti PAR,as a target gene of aromatic hydrocarbon receptor and estrogen receptor,plays an important role in the regulation of aromatic hydrocarbon,estrogen and other related signaling pathways,and is closely related to the occurrence and development of tumors.Studies have shown that Ti PAR is a susceptibility gene for ovarian cancer.Ti PAR may be a key target for the progression of ovarian cancer.Tumor cell epithelial-mesenchymal transition is an important driving factor for tumor cell metastasis.Wnt/β-catenin signaling pathway is one of the key pathways to induce tumor cell epithelial-mesenchymal transition.TiPARP may mediate the epithelial-mesenchymal transition of ovarian cancer cells and promotes the metastasis of ovarian cancer cells.Methods: The human ovarian cancer cell lines SKOV3 and HO8910 cells were transfected with TiPARP adenovirus and pc DNA3.1-sh TiPARP plasmid.CCK-8 and Transwell migration and invasion experiments were used to detect the proliferation,migration and invasion ability of cells after overexpression or knockdown.q RT-PCR and Western blot were used to detect TiPARP and tumor cell epithelial-mesenchymal transition related markers as well as Wnt/β-catenin signaling key factors in SKOV3 and HO8910 cells.Results: The proliferation,migration and invasion capabilities of SKOV3 and HO8910 cells are enhanced when TiPARP overexpress.While the capabilities will be fell down when TiPARP is knocked down.The epithelial-related marker E-cadherin was down-regulated in SKOV3 cell,while the mesenchymal-related marker N-cadherin was up-regulated when TiPARP overexpress;the opposite was true after knocking down the expression of TiPARP.With the overexpression of TiPARP,the key factor β-catenin in the Wnt/β-catenin signaling pathway increased,and the downstream genes c-myc and cyclin D1 were up-regulated.Conclusion: TiPARP promotes ovarian cancer cell epithelial-mesenchymal transition and activate Wnt/β-catenin signaling pathway.TiPARP promotes the metastasis of ovarian cancer may be closely related to cancer cell epithelial-mesenchymal transition and the activation of Wnt/β-catenin signaling pathway.These findings infer that TiPARP may be exploited as a therapeutic target for ovarian cancer patients.