Study Of The Role Of LATS1Gene On The Proliferation And Invasion Of Glioma Cells And Analysis Of Glioma Metabolomics

LATS1gene has been known as a repressor on cell proliferation. During the early stage ofmitosis, LATS1is phosphorylated to form a complex with CDC2which inhibits the activity ofH1histone kinase. Overexpression of LATS1can not only block G2-M by inhibiting CDC2kinase activity, but also induce apoptosis to inhibit tumor growth. Furthermore, methylation onLATS1promoter decreases LATS1expression. However, the role of LATS1in glioma remainselusive.Thus, in the first part of this study, I detected and compared the expression of LATS1in theglioma and normal brain tissue to study the relationship between WHO classification andprognosis. Meanwhile, I examined the expression of LATS1in glioma cells U251and studied therole of LATS1on cell proliferation, invasion and metastasis. The results provides a new basis forthe further study the mechanism underlying LATS1-mediated inhibition of cell growth.Metabolomic analysis of the changes of in vivo metabolites can be performed by means ofhigh-throughput analysis to find correlation and dynamic rules for the nature of metabolites andthe changes of quantity and pathophysiology. Tumorigenesis is affected by the interactionsbetween external environmental factors and internal ones. These interactions lead to qualitativeand quantitative changes of tumor genes and proteins, which will eventually be reflected in themetabolic changes of tumors. Compared with genomics and proteomics, metabolites can bemeasured with a high degree of automation, and the superiority of low cost for sample collectionand processing. Additionally, measurement of the changes of metabolite concentrations is moresensitive than that of biochemical reaction rates, which more directly reflects the progress of thedisease. The research on the metabolism of glioma malignant process is still in preliminary stage.Previously, metabolomic studies by the traditional collection of clinical samples fail to accuratelyidentify metabolites due to individual variations in samples and heterogeneity in tumor tissue orother factors. With the development of technology in cell culture, metabolomic studies on the in vitro enriched cultured tumor cells can not only overcome these shortcomings, but also has theadvantages of strong controllability, high stability, good reproducibility, etc.Therefore, in the second part of my study, I compared the malignant degree ofdifferent pathological grades of tumor tissue from cultured CHG-5and U87glioma celllines. Metabolonomics of these two cell lines were analyzed using600M1H-NMR assistedby the metabolic model. The results will have important scientific significance on revealingthe underlying molecular mechanism and potential clinical application values for diagnosisand treatment of glioma.