Radiosensitivity Of Glioma Cells Increased By Inhibiting Expression Of Aurora Kinase A

Purpose:Glioma is a common primary malignant brain tumor with a poor prognosis.Surgery combined with postoperative radiotherapy and chemotherapy is the standard treatment.The radiation sensitivity of tumors is a decisive factor affected the effectiveness of radiotherapy.Therefore,exploring key molecular targets regulated the radiosensitivity of tumor cells and developing new sensitization therapeutic schedules are crucial to improve the effectiveness of radiotherapy and the prognosis of patients.Aurora kinase A(AURKA)plays an important role in the growth and progression of tumor cells.The purpose of this study is to investigate the effect of AURKA on the prognosis of patients with glioma and those who have undergone radiotherapy,as well as to elucidate the effect of AURKA on the radiosensitivity of glioma cells through in vitro experiments,with the aim of providing a novel target and novel ideas for the treatment of glioma.Materials and methods:In this study,the Chinese glioma Genome Atlas(CGGA),GTEx and Gene Expression Profiling Interactive Analysis(GEPIA)databases were utilized to detect the expression of AURKA gene in both normal brain tissue and glioma cells.Prognostic factors of glioma patients were analyzed by univariate and multivariate Cox regression.The biological functions of AURKA gene were analyzed by using Gene Set Enrichment Analysis(GSEA),Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genome(KEGG).A glioma cell line with stable inhibition of AURKA expression(U251-sh AURKA)was constructed by lentivirus transfection.Wild U251 cells and U251-sh AURKA were irradiated with 0 Gy and 8 Gy,and the proliferation ability of glioma cells was observed by cell counting kit-8(CCK-8)and colony formation assay.Additionally,the expression of AURKA and the level of autophagy upon combined inhibition of AURKA expression with irradiation were detected by Western blot.Results:The comparison between CGGA database and GTEx database data showed that the expression of AURKA was apparently higher in glioma cells than in normal tissue(P < 0.001).The expression of AURKA increased along with the pathological grade(P< 0.01),and the expression of AURKA in recurrent glioma patients was higher than that in primary patients(P < 0.01).At the molecular pathological level,the expression of AURKA in patients with 1p19 q combined deletion and IDH mutant glioma was lower than that in patients without 1p19 q combined deletion and IDH wild-type glioma(P < 0.01;P < 0.01).The result of multivariate Cox regression analysis showed that the expression of AURKA was an independent prognostic factor for glioma patients.The higher the expression of AURKA,the worse the prognosis of glioma patients,and the same conclusion was also observed in patients treated with radiotherapy.The expression of AURKA can be used to judge the curative effect after radiotherapy,the lower the expression of AURKA,the better the effect of radiotherapy(P < 0.001),which indicated that AURKA can affect the radiosensitivity of glioma.GO,KEGG and GSEA analysis found that AURKA mainly acted on cell cycle and cell signal transduction.U251-sh AURKA was successfully constructed by lentivirus transfection.Compared with the control group,CCK-8 and colony formation assay revealed that the reduction of AURKA expression would inhibit cell proliferation(P = 0.001;P < 0.001),and the combination of radiation and inhibition of AURKA expression had the lowest cell proliferation rate and the best therapeutic effect,which indicated that inhibition of AURKA expression would increase the radiosensitivity of glioma(P < 0.001).Compared with the control group,inhibition of AURKA combined with radiation increased the autophagy level of glioma cells,a significant increase in the ratio of LC3 B II/I protein(P < 0.0001),and a decrease in the expression of p62 protein(P < 0.0001).Conclusion:Based on clinical data and in vitro cell experiments,the lower the expression of AURKA,the better the prognosis of glioma patients and the better the curative effect after radiotherapy.Inhibiting the expression of AURKA can increase the radiosensitivity of glioma cells,and this process has an increase in autophagy level.AURKA is expected to become a potential target for radiosensitivity of glioma and a biomarker for prognosis assessment.