HADHA Regulates The Malignant Biological Behavior Of Glioma Cells Via MDM2

Glioma is the most common malignant tumor of the central nervous system.The prognosis of glioma is characterized by high recurrence rate,high mortality rate and short survival time.Patients’ outcome is very dismal even after multidisciplinary and individualized treatment.Therefore,it is of great significance to explore the key molecules and pathways that participate in the initiation and progression of glioma,and to find potential therapeutic targets.It has been shown in the literature that the expression of HADHA in a variety of malignant tumors changes,which is closely related to the prognosis of patients and can be used as a prognostic marker for certain tumors.However,the role of HADHA in glioma has not been reported.In this study,we try to clarify the expression model of HADHA in glioma and the mechanism of HADHA in regulating the he malignant biological behavior of glioma cells.Our study can be divided into the following three parts:Part I The expression of HADHA in glioma and its correlation with the prognosis of patientsObjective: To explore the expression pattern of HADHA in glioma and its correlation with the prognosis of patients.Methods: Database searching and tissue chips were used to analyze the difference of HADHA expression between glioma and normal brain tissue.The relationship between the expression of HADHA and the prognosis of patients was evaluated by correlation and survival analysis.Results: The expression of HADHA in glioma is significantly higher than that in normal brain tissue.Its expression level increases with the patient’s age and tumor WHO grade.The higher the level of HADHA expression,the shorter the survival time of patients.Conclusion: HADHA is related to the progression of glioma and may be served as a potential therapeutic target.Part II The effect of HADHA on the malignant biological behavior of glioma cellsObjective: To investigate the effect of HADHA on the proliferation,migration,and apoptosis of glioma cells in vitro and tumorigenesis in vivo.Methods: Down-regulate the expression of HADHA in glioma cells,analyze the proliferation,migration,and apoptosis changes of glioma cells using high-throughput cell counting assay,flow cytometry,wound healing and Transwell assay.Observe the change of tumor growth in nude mice model.Results: Down-regulating HADHA significantly inhibited the proliferation and migration of glioma cells,and promoted apoptosis of such cells.Down regulation of HADHA inhibited tumor growth in the glioma transplantation model.Conclusion: HADHA promotes proliferation and migration of glioma cells,and inhibits apoptosis of such cells to accelerate the progression of glioma.Part III The mechanism of HADHA in regulating the malignant biological behavior of glioma cellsObjective: To explore the potential downstream molecules of HADHA in regulating the proliferation,migration and apoptosis of glioma cells.Methods: Gene expression profiling chip and bioinformatics analysis were used to predict the downstream molecules of HADHA.Co-immunoprecipitation and rescue experiment were applied to verify the relationship between HADHA and the predictive target.Results: Gene expression profiling chip and bioinformatics analysis predicted that MDM2 may be a target of HADHA.Co-immunoprecipitation confirmed that HADHA interacts with MDM2.Rescue experiment indicated that HADHA regulates the proliferation,migration and apoptosis of glioma cells via MDM2.Conclusion: HADHA regulates the malignant biological behavior of glioma cells through MDM2.