Role And Related Mechanism Of The N-acetylglucosaminyltransferase V In Ovarian Cancer Cells

Objective Ovarian cancer is the most common cause of death among all gynecologic malignancies.Recent statistical reports show that morbidity and mortality of ovarian cancer with dormant onset is increasing year by year.Because of non-specific symptoms and lacking effective diagnostic methods during early stage,most patients were diagnosed at their advanced stage and usually with metastasis to the whole pelvic and abdominal cavity.Although major advances have been made in operation and chemotherapeutic agents,the five-year survival rate of advanced ovarian cancer patients is still low.Therefore,exploring early diagnosis and new therapeutic targets of ovarian cancer is becoming the hot spot in current research.N-glycosylation is one of the most frequent manners of post-translational modification of proteins and is closely related to biological behavior of tumor cells.N-glycosylation is catalysed by various glycosyltransferases and Gn T-V is one of the most widely studied.Gn T-V has been reported to play a major role on proliferation,migration and invasion in various tumor cells.However,the function of it in ovarian cancer is unclear yet.Our study aimed to explore the effects of Gn T-V on proliferation,migration and invasion in ovarian cancer cells(A2780 and SKOV3).Then investigate the mechanism of Gn T-V in regulating ovarian cancer proliferation,migration and invasion,hoping to provided a theoretical basis for early diagnosis and new treatment strategy for ovarian cancer.Methods The lentiviral vector systems for knockdown and overexpression of Gn T-V was constructed and transfected ovarian cancer cells(A2780 and SKOV3).RT-PCR was conducted to evaluate the transfection efficiency.Cell growth(CCK-8),wound-healing,cell invasion(Transwell)assays were conducted to examine the effect of Gn T-V knockdown/ overexpression in A2780 and SKOV3.And then Western blot was adopted to observe the effect of Gn T-V knockdown/ overexpression on the expression of E-cadherin?laminin?MMP-2 and MMP-9 in A2780 and SKOV3.Results RT-PCR results showed that the expression of Gn T-V was significantly decreased after knockdown in A2780 and SKOV3.CCK-8 results showed that knockdown of Gn T-V promoted cell proliferation of ovarian cancer cells.Wound-healing results showed that knockdown of Gn T-V accelerated cell migration of ovarian cancer cells.Transwell results showed that knockdown of Gn T-V enhanced cell invasion of ovarian cancer cells.Flow cytometry results showed that knockdown of Gn T-V drived ovarian cancer cells to multiply more frequently.Western blot results showed that knockdown of Gn T-V decreased the expression of E-cadherin but increased the expression of MMP-2 and MMP-9.By contrast,overexpression of Gn T-V weakened the ability of proliferation,migration and invasion of ovarian cancer cells.In addition,overexpression of Gn T-V increased the expression of E-cadherin but decreased the expression of laminin,MMP-2 and MMP-9.Conclusion The expression of Gn T-V in ovarian cancer cells could inhibite proliferation,migration and invasion.And the biological function of Gn T-V was related to increasing the level of E-cadherin and decreasing the expression of laminin,MMP-2 and MMP-9.