CUX-1 Overexpression Correlates With The Tumor Proliferation And Predicts The Poor Prognosis Of Glioma Patients

Objective Human glioma is an enigmatic and invasive malignant intracranial tumor,and its high recurrence rate and poor prognosis seriously affect the human's quality of living and health.Cut like homeobox-1(CUX1)is expressed focus on the cortex upper layer and participates in DNA replication,cell cycle control and DNA repair.It has been proved to involve in the proliferation of various types of solid tumors.The aims of this study were to explore the relationship between CUX1 expression and the prognosis of glioma,as well as the related signaling pathways by performing a series of functional experiments and bioinformatic analysis.Methods Bioinformatic analysis was carried out to explore the differential expression and the effect on overall survival(OS)of patients with glioma in TCGA database.The expression of CUX-1 was measured by qRT-PCR/western/immunohistochemistry assays among divers WHO grade of glioma tissues and multiple cell lines.Moreover,their correlation with clinicopathological characteristics and survival prognosis of patients was also analyzed.Construction of cux-1 interference plasmid transfected cells,The effect of cux-1 on the proliferation and invasion of glioma cells was proved by invasion assay and CCK8 test.Finally,we performed GO / KEGG gene enrichment analysis to further predicted the CUX-1related target genes and induced-biological processes as well as associated signaling pathways through bioinformatics methods.Results: Bioinformatics analysis of TCGA database showed that there was gene differential expression of transcription factor CUX1 between normal brain tissues and glioma tissues,and the high expression of CUX-1 significantly shortened the overall survival period of patients(P< 0.05).The qRT-PCR and Western blot assays were performed to show that CUX-1 was highly expressed in gliomas and up-regulated with the increase of WHO grades at RNA and protein levels(P < 0.05).The results of IHC also demonstrated that the expression of transcription factor CUX-1 was significantly correlated with several tumor proliferation parameters(Ki-67,p53 mut,WHO grade)(P < 0.05).In addition,multivariate Cox regression and Kaplan-Meier curve indicated that the expression of CUX-1 could act as a novel biomarker and independent predictor of the prognosis of glioma patients,and the overall survival period of glioma patients with high expression of CUX-1 was significantly shortened.Finally,the role of CUX1 might be mediated via JAK-STAT pathway or other key regulator of cell cycle to promote proliferation,inflammation and chemotherapy resistance in glioma through GO/KEGG gene enrichment analysis.Conclusion: The expression of CUX-1 not only showed a tumor grade and clinicopathological factors-dependent pattern,but also distinguished glioma with poor prognosis,which may serve as a prognostic biomarker and potential therapeutic target in glioma.These data can be furthermore utilized through vitro techniques and extented in vivo models to elucidate the role of CUX1 in differentiation,proliferation and other malignancy-related biological behaviour.