Atractyloside Mimics Boris Knockdown To Induce Dna Damage In Colorectal Cancer Cells

The Brother of Regulator of Imprinted Sites (BORIS) is expressed abnormally in colorectal cancer and is predicted to be a potential diagnostic and prognostic target. However, little is known about BORIS-related signaling pathways and no bioactive drugs have been found to target BORIS. We screened the gene regulation panels of BORIS-silenced colorectal cancer cells by microarray assay and applied the regulated gene list in a connectivity map (CMap) database to screen for bioactive drugs which regulate gene panels similar to BORIS knockdown. Gene set enrichment analysis (GSEA) suggests a correlation between BORIS knockdown and apoptosis. Screening revealed atractyloside treatment as a drug similar to BORIS siRNA in regulating genes in colorectal cancer cells. Atractyloside treatment or BORIS knockdown induced the expression of XRCC4, which suggested DNA damage was induced by knockdown of the BORIS signaling pathway. H2A.X immunofluorescence stain indicated BORIS knockdown indeed created DNA damage. As atractyloside synergized with 5-Fluoruracil (5-FU) to suppress colorectal cancer cell proliferation, we concluded that the inhibition of BORIS downstream by atractyloside amplifies the effect of 5-FU by promoting DNA damage.