Knockdown of RAD18 inhibits glioblastoma development.

This study aimed at investigating the role of RAD18 in the regulation of glioblastoma development as well as the underlying mechanisms. The human glioblastoma U251 and U87MG cells were transfected with siRNAs specifically targeting RAD18, and the effects of knockdown of RAD18 on the viability, apoptosis, migration, and invasion of U251 and U87MG cells were investigated. Transcriptome sequencing of the siRNA-RAD18-tranfected and siRNA-NC-transfected U251 cells was performed, followed by bioinformatic analyses for sequencing data. The results showed that knockdown of RAD18 significantly inhibited cell viability, promoted apoptosis, and suppressed migration and invasion of U251 and U87MG cells. Bioinformatic analyses of sequencing data identified 1,051 differentially expressed genes (DEGs) (369 up- and 682 downregulated genes) in the siRNA-RAD18-transfected U251 cells compared with siRNA-NC-transfected U251 cells. Eleven DEGs, including nerve growth factor (NGF), colony-stimulating factor 2 (CSF2), matrix metallopeptidase 1 (MMP1), platelet-derived growth factor receptor α (PDGFRA), and heme oxygenase 1 (HMOX1), were identified as the hub nodes in protein-protein interaction (PPI) network. Moreover, the aforementioned 11 hub genes were significantly enriched in PI3K-Akt signaling pathway and GO functions associated with the extracellular region. Notably, quantitative real-time polymerase chain reaction further confirmed that the expression levels of NGF, CSF2, HMOX1, and MMP1 were significantly downregulated, while that of PDGFRA was markedly upregulated in the siRNA-RAD18-transfected U251 cells than in the siRNA-NC cells. In conclusion, the knockdown of RAD18 may inhibit glioblastoma development by regulating the expression of the aforementioned key DEGs.

Candidate genes and microRNAs for glioma pathogenesis and prognosis based on gene expression profiles.

Glioma is the most common malignant brain tumor, and the incidence of glioma demonstrates an upward trend. It is vital to elucidate the pathogenesis of glioma and seek effective therapies. The aim of the present study was to identify the potential gene markers associated with glioma based on GSE31262 gene expression profiles, and to explore the underlying mechanism of glioma progression by analyzing the gene markers. The microarray dataset GSE31262 was downloaded and neural stem cell samples (control group) and glioma samples (glioma group) were analyzed to identify the differentially expressed genes (DEGs) between the two groups. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using DAVID software. Subsequently, a protein­protein interaction (PPI) network was constructed and important modules were extracted from this network. Additionally, the miRNA­target regulatory network was established. In total, 1377 DEGs with P<0.01 and |log2 fold change| ≥2 were identified between the control and glioma groups. The DEGs that were upregulated in glioma samples compared with controls were primarily associated with functions such as the M phase and cell cycle pathway, while the downregulated genes were associated with functions such as nerve impulse and the axon guidance pathway. The results also indicated that certain DEGs, including cyclin­dependent kinase 1 (CDK1) and cadherin 1 (CDH1), had important roles in the PPI network. The MCODE tool in Cytoscape software was used to identify upregulated and downregulated modules in the PPI network, and 5 upregulated and 2 downregulated modules were extracted. Furthermore, the WebGestal online tool was used to identify potential interactions of the upregulated and downregulated genes with microRNAs (miRNA/miR), and miR­135A/B and its two targets, discs large MAGUK scaffold protein 2 and forkhead box O1 (FOXO1), had the highest number of connections in the miRNA­target regulatory network. In addition, cell division cycle 20 and FOXO1 were confirmed to be upregulated in U87 glioma cells compared with normal human astrocytes (HA1800) by reverse transcription­quantitative polymerase chain reaction. In conclusion, M phase function and the axon guidance pathway may be vital for glioma progression. In addition, CDK1 and CDH1 may be associated with the process of glioma. Furthermore, miR­135A/B, and the target FOXO1, may be potential therapy targets for glioma treatment.