Identification of key pathways and genes in vestibular schwannoma using bioinformatics analysis.

The aim of the present study is to identify novel promising marks and targets of diagnosis, therapy and prognosis for patients with vestibular schwannoma at the molecular level. The gene expression profiles of GSE54934, GSE39645 and GSE56597 datasets were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified by comparing between gene expression profiles of the vestibular schwannoma tissues and normal tissues. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were performed. The function and pathway enrichment analysis were performed for DEGs with DAVID. Reverse transcription-quantitative PCR were conducted to confirm the expression of BCL2, AGT, IL6 and ITGA2 in human Schwann cells and vestibular schwannoma cells. A total of 4,025, 1,1291 and 1,513 DEGs were identified from GSE54934, GSE56597 and GSE39645 datasets, respectively. GO and KEGG analysis showed that the mutual upregulated genes were mainly enriched in cell division, mitotic nuclear division, and transition of mitotic cell cycle, whilst mutual downregulated genes were enriched in chemical synaptic transmission, neurotransmitter transport, and synaptic vesicle membrane. Subsequently, 20 genes, including BCL2, AGT, IL6 and ITGA2 were selected as hub genes with high degrees after PPI network analysis. The significant differential expression of those genes were detected among vestibular schwannoma tissues compared with normal nerve tissues. In conclusion, BCL2, AGT, IL6 and ITGA2 are significantly higher expressed in vestibular schwannoma tissues compared with human Schwann tissues. The DEGs identified in the present study provide novel targets for the diagnosis and treatment of vestibular schwannoma.

T5224, RSPO2 and AZD5363 are novel drugs against functional pituitary adenoma.

We tested whether the drugs T5224, RSPO2, and AZD5363 exert therapeutic effects against functioning pituitary adenoma (FPA). We analysed the gene expression profiles of four FPA mRNA microarray datasets (GSE2175, GSE26966, GSE36314, and GSE37153) from the Gene Expression Omnibus database and identified genes differentially expressed in FPA vs control tissues. We then carried out Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network analyses. We also measured the difference in expression of hub genes between human normal pituitary cells and FPA cells using qRT-PCR. Our in vitro colony-formation and MTT assays showed that cell viability, number, and the size of clonogenicities were all lower in the presence of T5224, RSPO2, or AZD536 than in controls. Moreover, flow cytometry experiments showed that the incidence of apoptosis was higher in the presence of T5224, RSPO2, or AZD5363 than among controls, and was increased by increasing the doses of the drugs. This suggests these drugs could be used as therapeutic agents to treat FPA. Finally, we found that cFos, WNT5A, NCAM1, JUP, AKT3, and ADCY1 are abnormally expressed in FPA cells compared to controls, which highlights these genes as potential prognostic and/or therapeutic targets.