Deciphering the role of aleplasinin as a viable small molecule inhibitor of Siglec-15 in colorectal cancer progression

Aleplasinin is a small molecule inhibitor currently used in the treatment of Alzheimer’s disease. However, based on our docking analysis, we believe that it may be repurposed as a small molecule inhibitor targeting Siglec-15, a recent immune checkpoint protein and prominent oncogene implicated in cancer. We exhibited in vitro data demonstrating aleplasinin cytotoxicity on colorectal cancer cells and elucidated possible mechanisms of action, possibly hinting inhibition via lipid metabolism. Following total RNA extraction of SW480 colorectal cancer cells, RNA Illumina sequencing was conducted to compare the differential expression of gene targets between aleplasinin-treated and untreated conditions. Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis determined the enrichment of signalling pathways, biological processes, molecular functions and cellular components between the two conditions. From the analysis, the most downregulated gene identified was ACSL6, a prominent oncogene in CRC progression. Furthermore, data analysis revealed enriched Wnt signalling following treatment. This may highlight potential new approaches for repurposing currently available small molecule inhibitors for cancer treatment. The utilisation of aleplasinin in colorectal cancer treatment will provide insights into the molecular workings of Siglec-15-mediated tumour progression.