Cancer Promoting Effects Of MCM5 And Its Mechanism In Ovarian Cancer

Ovarian cancer is a prevalent malignancy in female reproductive system with an estimated 295 000 cases and 184 000 deaths worldwide in 2018.Although the incidence of ovarian cancer is lower than that of cervical cancer and endometrial cancer,the mortality of ovarian cancer stays at a high level and is highest.among female reproductive tract malignancies.Due to the insidious onset and lack of effective early screening techniques,majority of ovrian cancers are initially diagnosed at advanced stages,and therefore the patients lose the opportunity for radical surgery.There have been significant advances in treatment for the patients with varian cancer in recent years,most patients experience recurrence and metastasis within 2-3 years,and are prone to drug resistance after recurrence,leading to poor prognosis.However,recurrence and drug resistance would occur in this population.Demonstration of the origin of this desease and molecular mechanisms of its carcinogenesis,and screening molecular markers for early detection and prognostication,are of crucial significance.The Minichromosome Maintenance(MCM)proteins are essential for DNA replication,involving in the initiation and elongation of this process.They play vital roles in chromatin remodeling and checkpoint response as well.As a member of the MCM family,MCM5 overexpresses in various cancers.Overexpressed MCM5 correlated with tumor grade,.Our group’s previous study revealed that MCM5 was overexpressed in enmometrial serous carcinoma and promoted proliferation,migration and invasion.PurposeThe aim of this study is to study the expression and impact of MCM5 in ovarian cancer,especially in high-grade serous ovarian cancer.In addition,we aim to explore the potential value of MCM5 as a diagnostic marker for high grade serous carcinoma..Methods1.The expression of MCM5 in ovarian cancer and its effect on the prognosis of ovarian cancer patients were analyzed by analyzing data from TCGA,GSEA,and other public databases.2.Immunohistochemical staining was utilized to detect the expression of MCM5 in ovarian cancers and to analyze the correlation between MCM5 and clinicopathological parameters.3.Human ovarian cancer cell lines SKOV3 and HEY were selected to verify the mRNA and protein levels of MCM5 using qRT-PCR and Western blot.4.The effects of interference of MCM5 on the proliferation and viability of ovarian cancer cells were assessed through CCK8 and EdU experiments.5.The impact of interference of MCM5 on the clonogenic ability of ovarian cancer cells was determined by plate clonogenic assay.6.The influence of interference of MCM5 on the migration and invasion capabilities of ovarian cancer cells was assessed through scratching test and Transwell Chamber assays.7.Flow cytometry was employed to evaluate the effect of decreased MCM5 on ovarian cancer cell apoptosis.Results1.Bioinformatics analysis revealed that MCM5 mRNA in ovarian cancer was significantly elevated compared to normal ovarian tissue,and high MCM5 was associated with a low progression-free survival(P<0.01).2.Immunohistochemical results demonstrated that the expression of MCM5 in ovarian cancer was significantly higher than that in tubal epithelial tissue.Notably MCM5 was diffusely and strongly stained in high-grade serous ovarian cancer.MCM5 expression was significantly correlated with ER negativity and Ki67 index.3.CCK8,EdU,and plate cloning experiments indicated that interference of MCM5 with siRNA inhibited the proliferation,viability and clonality of ovarian cancer cells.4.Scratch and Transwell Chamber assays demonstrated that interference with MCM5 inhibited the migration and invasion of ovarian cancer cells.5.Flow cytometry revealed that apoptosis of ovarian cancer cells was decreased with interfering MCM5.Conclusions1.The expression of MCM5 is significantly increased in human ovarian cancers and high-grade serous carcinoma shows diffuse and strong staining of MCM5.In addition,high MCM5 is associated with a poor prognosis.2.In ovarian cancer,MCM5 promotes cancer progression by enhancing the proliferation,migration,and invasion of ovarian cancer cells.3.In ovarian cancer,MCM5 plays a role in promoting cancer by inhibiting cell apoptosis.4.MCM5 may serve as a potential prognostic marker for ovarian cancer and a novel diagnostic marker for high grade serous cancer.