Caspase-related apoptosis genes in gliomas by RNA-seq and bioinformatics analysis

Abstract

Gliomas are the most common malignant tumors of the brain. The aim of this study is to identify caspase-dependent apoptotic genes and uncover their potential regulatory mechanism in glioma progression. Human glioma cell line U251 was used. Three experiment groups were set as control group, H₂O₂ group (treated with H₂O₂) and caspase inhibitor group (treated with caspase inhibitor). For samples in each group, RNA-sequencing was performed on Illumina platform and differentially expressed genes (DEGs) between any two of the three groups were selected using NOISeq package. By overlapping analysis, the caspase inhibitor-related DEGs were further screened out, followed by enrichment analyses. Drugs associating with these genes were selected by WebGestalt. Protein-protein interaction (PPI) network analysis was conducted based on SRINIG database. A set of 105 caspase inhibitor-related DEGs were identified, which were significantly enriched in cellular components related functions (for example, TUBB2A, RPSA and RPL5); and metabolism related pathways (for example, PSMC3, KHSRP, RPL5 and RPSA). In addition, KHSRP and TUBB2A were significantly associated with several drugs such as cefotaxime, cefacetrile and netilmicin. Besides, PSMC3 and RPL5 were identified as crucial nodes in the PPI network. Several crucial genes in gliomas cells such as TUBB2A, RPSA, RPL5, PSMC3 and KHSRP were identified, which might play significant roles in apoptosis in a caspase-dependent manner. These genes might also involve in the regulation of metabolism related functions and pathways. KHSRP and TUBB2A might be novel targets of three drugs, cefotaxime, cefacetrile and netilmicin.

Keywords: Apoptosis; Caspase inhibitor; Differentially expressed gene; Enrichment analysis; Gliomas; Protein-protein interaction.