Role of the anti-glioma drug AT13148 in the inhibition of Notch signaling pathway

• Published in: Gene Vol. 573; no. 1; pp. 153 - 159
• Main Authors: Min, Weijie, Li, Yanan, Zhang, Yihui, Dai, Dongwei, Cao, Yiqun, Yue, Zhijian, Liu, Jianmin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2015
• Subjects: 2-Hydroxyphenethylamine - analogs & derivatives; 2-Hydroxyphenethylamine - pharmacology; Antineoplastic Agents - pharmacology; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; cell cycle; data collection; Differentially expressed genes; DNA replication; Drug target; drugs; gene expression; gene expression regulation; genes; Glioma; Glioma - metabolism; Glioma - pathology; Humans; microarray technology; Notch signaling pathway; Pyrazoles - pharmacology; Receptors, Notch - metabolism; signal transduction; MAML1-dn; MAML1; ROCK2; DTX1; EGFP; TFPI; NF-κB; DEGs; Differentially expressed genes; IMPA1; FDR; NCBI; KDR; KEGG; ASL; ACSS1; PDGFRB; Notch signaling pathway; STAT3; GO; Drug target; GS; PCA; GEO; GBMg; Glioma; GCLM
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2015.07.033

To investigate the drug targets related to Notch signaling pathway for glioma treatment. Gene expression profiles GSE44561, GSE48079 and GSE22772GSE48079GSE22772 of glioma cells samples with activated Notch signaling pathway and control samples were downloaded from Gene Expression Omnibus database to screen the differentially expressed genes (DEGs) using limma package. GO (Gene Oncology) function and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses were conducted using DAVID tools to predict the underlying function of these DEGs. Sequentially, drug target genes recorded in DrugBank database were collected and matched with the selected DEGs to identify the potential drug targets for glioma. Further, these targets were verified by the screened DEGs in the anti-glioma drug (AT13148) treated samples of microarray data of GSE38008. A total of 75,645,497 DEGs were respectively identified in GSE44561, GSE48079 and GSE22772GSE48079GSE22772 datasets and these DEGs could well distinguish the glioma samples from controls. The DEGs were mainly enriched in classical functions and pathways, such as cell cycle, and DNA replication. A total of 122 DEGs were found to be potential drug targets for glioma, among which GLIPR1 was targeted by drug XL820, PDGFRB and KDR were targeted by SOT-107. Efficacy validation of the other 119 drug targets by GSE38008 data showed that ACSS1, ASL, GCLM, ROCK2, IMPA1, and TFPI may be targeted by the anti-glioma drug of AT13148. AT13148 may inhibit glioma progression by suppressing the Notch signaling genes, including GLIPR1, PDGFRB, ACSS1, and ASL. •Several Notch signaling related genes were identified in glioma.•Notch related genes may participate in glioma by affecting cell cycle.•122 genes were found to be potential drug targets for glioma.•AT13148 drug has been demonstrated to exert anti-glioma effects.