ABSTRACT
Objective: To investigate the mechanism of depression by Sini Powder. Methods: The chemical composition and targets of Bupleuri Radix, Paeonia Radix Alba, Aurantii Fructus Immaturus, and Glycyrrhizae Radix et Rhizoma were searched by the analysis of traditional Chinese medicine system pharmacology platform (TCMSP). Depression related genes were screened from OMIM, TDD, Drugbank, and Digsee multiple databases. The target corresponding genes were searched through UniProt, GeneCards, and PubMed database query and then Cytoscape 3.2.1 was used to build compound-targets (genes) networks, protein interaction (PPI) filter core targe; At last, the enrichment of gene ontology (GO) function analysis by DAVID based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out, and the mechanism of its action research was predicted. Results: The compound-target network contained 121 compounds and the corresponding 259 targets, and the key targets involved PTGS2, CALM1, ESR1, HSP90AA1, AR, etc. The PPI core network contained 15 proteins, key proteins involved in CASP3, CHRM2, CYP3A4, and etc. The function enrichment analysis of GO was 375 (P < 0.05), of which there were 307 biological processes (BP), and 37 related items of cell composition (CC), and 31 molecular function (MF) items. 37 related items of cell composition (CC), and 31 molecular function (MF) items. There were 37 signal pathways (P < 0.05) in KEGG pathway enrichment screening, involving neuroactive ligand-receptor interaction, dopaminergic synapse, IL-17 signaling pathway and so on. Conclusion: The active components in Sini Powder play an antidepressant role by acting on 15 key targets such as CASP3, CHRM2, DRD1 to regulate multiple signaling pathways.
ABSTRACT
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death. This study was designed to identify key genes associated with DIPG. METHODS: The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by limma package. Functional and pathway enrichment analyses were performed by the DAVID tool. Protein-protein interaction (PPI) network, and transcription factor (TF)-microRNA (miRNA)-target gene network were constructed using Cytoscape. Moreover, the expression levels of several genes were validated in human glioma cell line U251 and normal glia HEB cells through real-time polymerase chain reaction (PCR). RESULTS: A total of 378 DEGs were screened (74 up-regulated and 304 down-regulated genes). In the PPI network, GRM1, HTR2A, GRM7 and GRM2 had higher degrees. Besides, GRM1 and HTR2A were significantly enriched in the neuroactive ligand-receptor interaction pathway, and calcium signaling pathway. In addition, TFAP2C was a significant down-regulated functional gene and hsa-miR-26b-5p had a higher degree in the TF-miRNA-target gene network. PCR analysis revealed that GRM7 and HTR2A were significantly downregulated while TFAP2C was upregulated in U251 cells compared with that in HEB cells (p < 0.001). GRM2 was not detected in cells. CONCLUSIONS: GRM1 and HTR2A might function in DIPG through the neuroactive ligand-receptor interaction pathway and the calcium signaling pathway. Furthermore, the TFAP2C and hsa-miR-26b-5p might play important roles in the development and progression mechanisms of DIPG.