In this study, we used bioinformatics analysis to obtain DEGs between glioma and normal brain tissue samples based on GSE50161 database. 1882 DEGs were identified and the function of these differential genes were mainly concentrated in the cell division, cell adhesion, nervous system development and neurotransmitter secretion. DEGs with significantly differential expression were chose and PPI network was constructed. Among them, WEE1, CDK1, PBK, CCNB2, NUSAP1 and CAMK2A genes were obviously associated with cell cycle process. Analysis of the PPI network and PPI core sub-network demonstrated that CDK1, TPO2A, NUSAP1, PBK and CHEK1which had higher degrees in the network were enriched in the cell cycle signaling pathway and interacted with each other.
The protein encoded by the Cyclin-dependent kinase 1(CDK1) gene regulated cell cycle and RNA transcription19. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. This allows cancer cell to enter the S phase in time from G1 phase, and maintain a strong ability to divide20. Studies had found that CDK1 promoted cell proliferation and survival via phosphorylation and FoxO1 transcription factor inhibition21.
WEE1 belongs to a family of protein kinases involved in the terminal phosphorylation and inactivation of cyclin-dependent kinase 1-bound cyclin B, resulting in G2 cell cycle arrest in response to DNA damage22. WEE1 is expressed at high levels in various cancer types including breast cancers, leukemia, melanoma, and adult and pediatric brain tumors. And recent study demonstrated that WEE1 phosphorylated and inactivated the CDK1–cyclin B complex on tyrosine 15, resulting in cell-cycle arrest in G2, allowing time for DNA repair23. WEE1 may serve a key role during the progression of gliomas. Nucleolar and spindle-associated protein (NUSAP1), as a microtubule and DNA-binding protein, play key roles in cell-cycle progression and cytokinesis24. Several recent studies have indicated that NUSAP1 has been involved in tumor progression and expansion, such as breast cancer, hepatocellular carcinomas, and pancreatic adenocarcinoma25–27. The down-regulation of NUSAP1 had been proved that it had a regulatory effect on the progression of human glioma cells G2/ M and cell proliferation in vivo24. Therefore, the gene may contribute to the development of gliomas.
The PDZ binding kinase (PBK) encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. And it plays a major role in proliferation and in safeguarding mitotic fidelity in cancer cells and drives tumorigenesis and metastasis28. CHEK1, another up-regulated pro-oncogene identified in the present study, encodes a checkpoint kinase of cell cycle. And studies have found that the overexpression of CHEK1 was related to the poor prognosis of ovarian cancer29. All of these genes identified by bioinformatics analysis may have a great significance to the study of regulation about the cell cycle process on glioma.
The protein encoded by CAMK2A gene belongs to the serine/threonine protein kinases family, and to the Ca (2+)/calmodulin-dependent protein kinases subfamily. At present, the role of this gene in the tumor has not been studied. CAMK2A are the most abundant protein in the brain and are shown to be crucial for normal neurodevelopment in humans30. Studies have found that the loss of CAMK2A is fatal to the brain development process31. However, the key role of CAMK2A is currently poorly understood. Our research found that this gene
may participated the cell cycle process of glioma and was down-regulated.
However, the present study has a number of limitations. Our results were simply to screen out genes that have significant differences in expression between glioma and normal samples and then may play an important role in cell cycle processes. More biology experiments are needed to confirm the function of these identified genes in gliomas.