Functional And Mechanism Research Of Spindle And Kinetochore Associated Complex Subunit 1 In Glioma

Tumors of central nervous system(CNS)are major contributors to human cancer mortality.According to the epidemiological reports,glioma accounting for more than 50%of primary intracranial tumors in all age groups.Glioma has attracted much attention because of its high morbidity and mortality in central nervous system tumors,and it have an extremely high recurrence rate after surgical treatment.Despite of the current standard therapy including sulrgical resection combined chemotherapy and radiotherapy(STUPP protocol),the therapeutic effect is barely ameliorated to glioblastoma(GBM)which account for about 60%-70%of gliomas.The mean survival time of patients with GBM was prolonged from 12.1 months to 14.6 months after treatment,and the 2-year survival rate was 26.5%.Due to surgical resection can only excise the solid part of the tumor showed on image,but there are tumor cells remaining in normal brain tissue outside of the tumor entity as revealed by the imaging,glioma is hard to cure.Glioma often recurrence on the margins of the incision.Most of the patients die within 2 years after recurrence.Therefore,it is an important direction to study the malignant biological behavior of glioma including high proliferation and invasion.And it will help to carry out targeted treatment of glioma.Spindle and kinetochore associated complex subunit 1(SKA1)is a recently discovered protein that related to the process of cell mitosis.SKA1 was found to be closely related to the occurrence and development of many malignant tumors.In oral squamous cell carcinoma,lung cancer,gastric cancer,hepatocellular carcinoma and bladder cancer,the researchers found abnormal high expression of SKAI.In these tumors,SKA1 affects not only the cell proliferation,but also cell migration and invasion.The research of SKA1 in glioma has rarely been reported.In this study,we focused on the expression of SKA1 in glioma and its clinical significance,explored the impact of SKA1 on the biological function of glioma cells,and performed a preliminary study of molecular mechanism which SKA 1 effected in glioma cells.Chapter 1.The expression of SKA1 in glioma and its clinical significanceMethods:We analyzed the expression levels and clinical significance of SKAI in glioma and normal brain tissues using data deposited in online public database.To further confirm our founds,glioma specimens obtained from surgical resection were used for verification.Results:The expression of SKA1 in glioma was positively correlated with pathological grade.SKA1 was highly expressed in GBM and could be used as a molecular marker for diagnosis of GBM.Meanwhile,glioma patients with high SKAI expression have poorer prognoses.Chapter 2.The study on cell biological function of SKA1 in gliomaMethods:To determine the biological functions of SKA1 in glioma,lentiviral shRNA vector were used to specifically and stably knock down the expression of SKA1 in glioma cell lines.Multiple assays were performed to determine the function of SKA1 on glioma cell proliferation,migration and invasion ability in vitro and in vivo.Results:Particularly,SKA1 facilitates proliferation,migration as well as invasion in glioma cell lines.Furthermore,it is demonstrated that suppression of SKA I inhibited glioma proliferation in vivo.Chapter 3.The preliminary study of molecular mechanism which SKA1 effected in glioma cells.Methods:Bioinformatics analysis was used to reveal the biological processes and the cell signaling pathways which SKA1 effected in glioma.Then Western blot was used to verify the results.Results:SKA1 mainly participates in the regulation of cell cycle and Wnt/p-Catenin signaling pathway in gliomas.The expression of proteins involved in cell proliferation,migration and invasion were changed after SKA1 suppressed in glioma cells.