Role of cancer stem cells in racial disparity in colorectal cancer

Abstract

Although African-Americans (AAs) have a higher incidence of colorectal cancer (CRC) than White people, the underlying biochemical mechanisms for this increase are poorly understood. The current investigation was undertaken to examine whether differences in self-renewing cancer stem/stem-like cells (CSCs) in the colonic mucosa, whose stemness is regulated by certain microRNAs (miRs), could partly be responsible for the racial disparity in CRC. The study contains 53 AAs and 47 White people. We found the number of adenomas and the proportion of CD44⁺CD166⁻  CSC phenotype in the colon to be significantly higher in AAs than White people. MicroRNAs profile in CSC-enriched colonic mucosal cells, expressed as ratio of high-risk (≥3 adenomas) to low-risk (no adenoma) CRC patients revealed an 8-fold increase in miR-1207-5p in AAs, compared to a 1.2-fold increase of the same in White people. This increase in AA was associated with a marked rise in lncRNA PVT1 (plasmacytoma variant translocation 1), a host gene of miR-1207-5p. Forced expression of miR-1207-5p in normal human colonic epithelial cells HCoEpiC and CCD841 produced an increase in stemness, as evidenced by morphologically elongated epithelial mesenchymal transition( EMT) phenotype and significant increases in CSC markers (CD44, CD166, and CD133) as well as TGF-β, CTNNB1, MMP2, Slug, Snail, and Vimentin, and reduction in Twist and N-Cadherin. Our findings suggest that an increase in CSCs, specifically the CD44⁺CD166⁻ phenotype in the colon could be a predisposing factor for the increased incidence of CRC among AAs. MicroRNA 1207-5p appears to play a crucial role in regulating stemness in colonic epithelial cells in AAs.

Although the incidence of and mortality from colorectal cancer (CRC) is higher among the African Americans (AAs) than White people, the underlying biochemical mechanism(s) for this racial disparity are poorly understood. The present investigation is aimed at elucidating the regulatory mechanisms for differences in cancer stem/stem-like cells (CSCs) in colonic neoplasia between AAs and White people by evaluating the role of microRNAs, specifically the microRNA-1207-5p, which is shown to be upregulated in CRC. microRNA (miR)-1207-5p plays a critical role in regulating stemness in colon CSCs and suggests a potential molecular mechanism for the increased risk of CRC among AAs.

from Cancer via ola Kala on Inoreader http://ift.tt/1V6VfSr
via IFTTT