Microarray analysis points to LMNB1 and JUN as potential target genes for predicting metastasis promotion by etoposide in colorectal cancer

Abstract Etoposide is a second-line chemotherapy agent widely used for metastatic colorectal cancer. However, we discovered that etoposide treatment induced greater motility potential in four colorectal cancer cell lines. Therefore, we used microarrays to test the mRNA of these cancer cell lines to investigate the mechanisms of etoposide promoting colorectal cancer metastasis. Differentially expressed genes (DEGs) were identified by comparing the gene expression profiles in samples from etoposide-treated cells and untreated cells in all four colorectal cancer cell lines. Next, these genes went through the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Among the top 10 genes including the upregulated and downregulated, eight genes had close interaction according to the STRING database: FAS, HMMR, JUN, LMNB1, MLL3, PLK2, STAG1 and TBL1X. After etoposide treatment, the cell cycle, metabolism-related and senescence signaling pathways in the colorectal cancer cell lines were significantly downregulated, whereas necroptosis and oncogene pathways were significantly upregulated. We suggest that the differentially expressed genes LMNB1 and JUN are potential targets for predicting colorectal cancer metastasis. These results provide clinical guidance in chemotherapy, and offer direction for further research in the mechanism of colorectal cancer metastasis.