Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [CACO]

Human-specific changes in specific Siglecs is one of the reasons put forth as molecular mechanisms that could explain human proneness to developing cancers. The SIGLEC12 gene, which encodes the Siglec-XII protein mainly found on epithelial cells, has a fixed homozygous missense mutation in a critical arginine renders unable to recognize its natural ligand. Additionally, the gene harbors a polymorphic frameshift mutation that eliminates expression of the full-length protein in most humans. We hypothesized that dysfunctional Siglec-XII is involved in cancer progression in humans' epithelia. Here we report that the forced expression of human Siglec-XII in caco-2 cells showed that differentially expressed genes in Siglec-XII cells were enriched for diverse bioenergetic processes. Overall design: To explore the significance of human Siglec-XII in the progression of CRCs, we used Siglec-XII non-expressing Caco-2 cell line. Cells were transfected with either pCDNA-3.1-SIGLEC12 or with empty vector (control), forcing them to exogenously express full-length Siglec-XII and stable clones were selected. We then performed gene expression profiling analysis using data obtained from RNA-seq of three cultures for each condition.