Transcriptional Profiling Reveals the Regulatory Role of CXCL8 in Promoting Colorectal Cancer

Abstract

C-X-C motif chemokine ligand 8 (<i>CXCL8</i>) is involved in tumor proliferation, migration, and invasion. However, the function of <i>CXCL8</i> in colorectal cancer (CRC) is controversial. Here, we analyzed RNA-sequencing (RNA-seq) data to identify differentially expressed genes and pathways according to gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with CRC. The levels of the mRNA encoding <i>CXCL8</i> were significantly increased in early and advanced stages of CRC, as well as in metastases and nonmetastasis cases using RNA-seq analysis (n = 91). These findings were consistent with immunohistochemical analysis of <i>CXCL8</i> expression (n = 87). Protein-protein interaction (PPI) prediction combined with transcriptional profiling data revealed that <i>CXCL8</i> levels positively correlated with cAMP responsive element binding protein 1 (<i>CREB1</i>)/ribosomal protein S6 kinase B1 (<i>RPS6KB1</i>) expression, which promotes cell proliferation and differentiation in high expression, while inversely correlated with the expression of Bcl2 associated agonist of cell death (<i>BAD</i>) protein to inhibit apoptosis during the progression of CRC. These findings provide compelling clinical and molecular evidence to support the conclusion that <i>CXCL8</i> contributes to the genesis and progression of CRC.