Role of lamin A/C gene in the malignant biological behavior of glioblastoma
Objective:To study the expression characteristics of lamin A/C(LMNA)gene in human glioblastoma and the mechanisms of its roles in the pathogenesis of glioblastoma.Methods:The study analyzed the expression of LMNA gene in glioblastoma and its correlation with patient prognosis in the public databases of TCGA.The LMNA gene sh-RNA virus was constructed to generate stable LMNA knockdown strains of glioma cell line U87.Then the clone formation and 3D spheroidization experiments were conducted on the LMNA knockdown strains of U87 and its control group to detect the impact of LMNA gene on cell proliferation and spheroidization ability.The resistance of LMNA knockdown U87 to temozolomide was detected through temozolomide treatment assay.The inhibitory effect of LMNA knockdown on glioblastoma growth and proliferation in vivo was detected through intracranial tumor implantation experiments in nude mice.Results:TCGA data showed that the expression level of LMNA in glioblastoma tissue was significantly higher than that in normal tissue,and it was negatively correlated with patient survival prognosis.The expression level of LMNA was positively correlated with the malignancy of tumor cells.LMNA knockdown significantly reduced the clone generation and spheroidization ability of U87 cell line,while it significantly increased the sensitivity of U87 cell line to temozolomide.The intracranial tumor implantation experiments in nude mice showed that the U87 cell line with LMNA knockdown significantly reduced the tumor volume in the mouse brain and improved their survival time.Conclusions:LMNA gene expression is increased in glioblastoma and negatively correlated with patient survival.LMNA gene knockdown can inhibit the proliferation of U87 glioma cell line and increase its sensitivity to temozolomide,making it as a potential target for glioblastoma treatment.
国家科技期刊平台
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