Abnormal expression of HOXD11 promotes the malignant behavior of glioma cells and leads to poor prognosis of glioma patients

PeerJ

Wang Zhang¹  Bo Pang²  Zhendong Liu³  Ang Li³  Yanzheng Gao³  Hongbo Wang⁴  Bo Zhang⁴  Cheng Zhang⁵  Xiaoyu Lian⁶  Jialin Wang⁶  Binfeng Liu⁶  Zhishuai Ren⁶  Yanbiao Wang⁶ 

[1] Department of Neurosurgery of the First Affiliate Hospital of Harbin Medical University, Harbin,Heilongjiang, China;Department of Neurosurgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, China;Department of Surgery of Spine and Spinal Cord, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China;Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, China;North Broward Preparatory School, Nord Anglia Education, Coconut Creek, FL, United States of America;Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, China;

关键词: Glioma;    HOXD11;    Biomarker;    Proliferation;    Invasion;    Cell cycle;   

DOI  :  10.7717/peerj.10820

来源: DOAJ

【 摘 要 】

Background Homeobox 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 methods Obtain 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. Results The 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. Conclusions HOXD11 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.

【 授权许可】

Unknown