Single Nucleotide Polymorphism Facilitated Down-Regulation of the Cohesin Stromal Antigen-1: Implications for Colorectal Cancer Racial Disparities

Publication date: March 2018
Source:Neoplasia, Volume 20, Issue 3
Author(s): Somenath Datta, Richard M. Sherva, Mart De La Cruz, Michelle T. Long, Priya Roy, Vadim Backman, Sanjib Chowdhury, Hemant K. Roy
The biological underpinnings for racial disparities in colorectal cancer (CRC) incidence remain to be elucidated. We have previously reported that the cohesin SA-1 down-regulation is an early event in colon carcinogenesis which is dramatically accentuated in African-Americans. In order to investigate the mechanism, we evaluated single nucleotide polymorphisms (SNPs) for association with SA-1-related outcomes followed by gene editing of candidate SNP. We observed that rs34149860 SNP was significantly associated with a lower colonic mucosal SA-1 expression and evaluation of public databases showed striking racial discordance. Given that the predicted SNP would alter miR-29b binding site, we used CRISPR knock-in in CRC cells and demonstrated that the SNP but not wild-type had profound alterations in SA-1 expression with miR-29b inhibitor. This is the first demonstration of high-order chromatin regulators as a modulator of racial differences, risk alteration with SNPs and finally specific modulation by microRNAs.



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