Abstract
BackgroundHomeobox D11 (HOXD11) plays an important role in a variety of cancers, but its precise role in gliomas remains unclear. This study aimed to explore the relationship between HOXD11 and gliomas by combining bioinformatics methods with basic experimental validation.Materials and methodsObtain gene expression information and clinical information of glioma and non-tumor brain tissue samples from multiple public databases such as TCGA (666 glioma samples), CGGA (749 glioma samples), GEPIA(163 glioblastoma samples and 207 normal control samples), GEO (GSE4290 and GSE15824). Nine cases of glioma tissue and five cases of normal control brain tissue were collected from the clinical department of Henan Provincial People’s Hospital for further verification. A series of bioinformatic analysis methods were used to confirm the relationship between HOXD11 expression and overall survival and clinical molecular characteristics of patients with glioma. RT-qPCR was used to verify the change of expression level of HOXD11 in glioma cells and tissues. MTT assay, colony formation assay, wound-healing assay, immunofluorescence staining, flow cytometry and western blotting were used to detect the effect of HOXD11 on the biological behavior of glioma cell line U251.ResultsThe high expression of HOXD11 was significantly related to age, World Health Organization (WHO) grade, chemotherapy status, histological type, and even 1p19q codeletion data and isocitrate dehydrogenase (IDH) mutation. HOXD11, as an independent risk factor, reduces the overall survival of glioma patients and has diagnostic value for the prognosis of glioma. Gene Set Enrichment Analysis (GSEA) showed that HOXD11 was significantly enriched in cell signaling pathway such as cell cycle, DNA replication and so on. Finally, we confirmed that the knockout of HOXD11 can inhibit the proliferation and invasion of U251 glioma cells, and change the biological behavior of tumor cells by preventing the progression of cell cycle.ConclusionsHOXD11 may be used as a candidate biomarker for the clinical application of targeted drug and prognostic assessment treatment of glioma. In addition, This study will help to explore the pathological mechanism of glioma.
Highlights
Gliomas are one of the most common primary intracranial neoplasms, accounting for 81% of intracranial neoplasms (Ostrom et al, 2014)
By analyzing the data of glioma tissues and cell lines microarrays obtained from GEO database, it was found that Homeobox D11 (HOXD11) was highly expressed in both glioma tissues and cell lines, as shown in Figs. 1B and 1C
The results showed that HOXD11 was highly expressed in glioma tissues and cell lines compared with normal brain tissues and human astrocytes, as shown in Figs. 1D and 1E
Summary
Gliomas are one of the most common primary intracranial neoplasms, accounting for 81% of intracranial neoplasms (Ostrom et al, 2014). Scientists have adopted new treatment methods, such as immunotherapy and photodynamic therapy, to overcome current limitations (Kong, Wang & Ma, 2018; Zavadskaya capital Te, 2015). These new treatments have not yet completely improved the prognosis of gliomas. A series of bioinformatic analysis methods were used to confirm the relationship between HOXD11 expression and overall survival and clinical molecular characteristics of patients with glioma. RT-qPCR was used to verify the change of expression level of HOXD11 in glioma cells and tissues.
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