Fan QW, et al. – Experts employed a combined method of microarray and bioinformatics analysis, and investigated the anticancer effects of a novel proteasome inhibitor, ixazomib, on colorectal cancer (CRC). The proliferation of human CRC SW620 cells was inhibited by the novel proteasome inhibitor ixazomib. Via targeting the expression of differentially expressed genes (DEGs), such as HSPA6, APCDD1, TP53, and JUN, and affecting the signaling pathways including apoptosis and cell cycle pathway, the novel proteasome inhibitor ixazomib exerted anticancer effects. This outcome demonstrated the promising potential of ixazomib for CRC therapy.

Methods

• They examined cell proliferation by Cell Counting Kit-8 (CCK-8) assay for SW620 cells treated with different concentrations of ixazomib and different treatment times.
• For six samples, including three samples of SW620 cells untreated with ixazomib and three samples of SW620 cells treated with ixazomib, the microarray analysis was conducted.
• The Linear Models for Microarray data (LIMMA) package in R language determined the differentially expressed genes (DEGs) between untreated and treated samples.
• They conducted the Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the DEGs using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and KEGG Orthology-Based Annotation System (KOBAS) online tool.
• The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct the protein–protein interaction (PPI) network, and module analysis was performed for the PPI network.

Results

• As per the observations, ixazomib could inhibit the proliferation of SW620 cells in a dose-dependent and time-dependent manner.
• They delineated a total of 743 DEGs, including 203 upregulated DEGs such as HSPA6 and 540 downregulated DEGs such as APCDD1.
• In addition, eighty-three GO terms were enriched for DEGs, which were mainly related to protein folding, apoptotic process, transcription factor activity, and proteasome.
• Including pathway of apoptosis and cell cycle, thirty-seven KEGG pathways were perturbed.
• This study screened out forty-six hub genes, such as TP53, JUN, and ITGA2.
• Three modules with important functions were mined from the PPI network.