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TRIM29 Promotes The Proliferation And Tumorigenicity Of Glioma And The Underlying Mechanism

Posted on:2019-02-17Degree:MasterType:Thesis
Country:ChinaCandidate:Y T WangFull Text:PDF
GTID:2404330623956954Subject:Neurosurgery
Abstract/Summary:PDF Full Text Request
BackgroundGliomas are the most common primary brain tumor in the adult,with an average incidence of 4-5 per 100,000 people per year,and their mortality is significantly higher than other brain tumors.Although the development of neurosurgery treatment and radiation therapy has made considerable progress in the past few decades,as the most common primary tumor of the central nervous system,the median survival time of gliomas is only about 15 months..Therefore,it is particularly important to study the mechanism of glioma development and provide a theoretical basis for finding new targets for the treatment of glioma.TRIM29(tripartite motif-29),also known as ATDC,is a member of the TRIM protein family,which consists of more than 70 members.The TRIM protein family is characterized by a series of conserved domain structures,including B-box type 1(B1),B-box type 2(B2)and RING finger and coiled helix(RBCC)domain motifs.Current research shows that the TRIM family is involved in regulating a variety of biological processes,such as cell development,differentiation,apoptosis,and tumorigenesis.The TRIM29(ATDC)gene is located on chromosome 11q23 and was originally thought to be an ectopic gene in telangiectasias of genetic disease ataxia and was found to increase radiation resistance in cells.It has been reported that TRIM29 plays an important role in many kinds of tumors.It is closely related to the proliferation,migration and tumorigenicity of tumor cells,but it has not yet been clearly reported and studied in gliomas.PurposeThe purpose of this study was to investigate the relationship between the expression of TRIM29 in gliomas and clinical characteristics of patients,and the effect of TRIM29 on the proliferation,migration and tumorigenicity of glioma cells,and to explore the underlying mechanism.Method1.The expression of TRIM29 protein in 56 cases of glioma tissue and normal brain tissue was detected by immunohistochemical method.The relationship between TRIM29 protein expression and clinicopathological features in glioma tissues was analyzed.The expression profile of TRIM29 protein was detected by Western blot in common glioma cell lines(A172,LN-229,U-87 MG,U-118MG).2.Stably knocked shTRIM29 cells were obtained using RNA interference technology.Transwell,MTT,BrdU,and soft agar cloning assays were used to test the effect of TRIM29 on the migration and proliferation of glioma cells.3.Through the construction of a subcutaneous tumorigenesis model in nude mice,the effect of TRIM29 on the proliferation and tumorigenicity of glioma cells in vivo was examined.4.Western blot was used to detect the effect of TRIM29 on AKT signaling pathway-associated proteins,and the intrinsic mechanism of TRIM29 on glioma proliferation and colony formation was explored.Conclusion1.The expression of TRIM29 in glioma tissues was positively correlated with the WHO staging of gliomas.At the same time,TRIM29 was expressed in glioma cell lines,and the expression of TRIM29 was significantly increased in U-87 MG cells with higher degree of malignancy.Suggesting that high expression of TRIM29 is closely related to the malignant degree of glioma2.Down-regulate protein expression of TRIM29 can inhibit the proliferation and migration of glioma cells3.Down-regulation of TRIM29 expression can inhibit the proliferation and tumorigenicity of glioma cells in vivo,indicating that TRIM29 is a key factor affecting the development of gliomas.4.TRIM29 may regulate glioma cell proliferation and colony formation through AKT signaling pathway...
Keywords/Search Tags:TRIM29, glioma, proliferation, migration, tumorigenicity
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