Single Nucleotide Polymorphism Facilitated Down-Regulation of the Cohesin Stromal Antigen-1: Implications for Colorectal Cancer Racial Disparities
| Autor: | Richard Sherva, Vadim Backman, Sanjib Chowdhury, Somenath Datta, Michelle T. Long, Mart Dela Cruz, Priya Roy, Hemant K. Roy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Original article Cancer Research Stromal cell Carcinogenesis Chromosomal Proteins Non-Histone Colorectal cancer Down-Regulation Cell Cycle Proteins Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Cell Line Tumor microRNA medicine Humans CRISPR SNP Genetic Predisposition to Disease Binding Sites Cohesin Nuclear Proteins HCT116 Cells medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Chromatin MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Colorectal Neoplasms |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 20, Iss 3, Pp 289-294 (2018) Neoplasia (New York, N.Y.) |
| ISSN: | 1522-8002 1476-5586 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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