title: 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.
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.|Department of Internal Medicine, Wayne State University, Detroit, Michigan, 48201.
authors.forename: Lulu
authors.initials: L
authors.lastname: Farhana
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.
authors.forename: Fadi
authors.initials: F
authors.lastname: Antaki
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Anees
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.|Karmanos Cancer Center, Detroit, Michigan, 48201.|Department of Internal Medicine, Wayne State University, Detroit, Michigan, 48201.
authors.forename: Pratima
authors.initials: P
authors.lastname: Nangia-Makker
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Judd
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.|Department of Internal Medicine, Wayne State University, Detroit, Michigan, 48201.
authors.forename: Timothy
authors.initials: T
authors.lastname: Hadden
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.|Department of Pathology, Medicine, Wayne State University, Detroit, Michigan, 48201.
authors.forename: Edi
authors.initials: E
authors.lastname: Levi
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.
authors.forename: Farhan
authors.initials: F
authors.lastname: Murshed
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.|Department of Internal Medicine, Wayne State University, Detroit, Michigan, 48201.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Karmanos Cancer Center, Detroit, Michigan, 48201.|Department of Internal Medicine, Wayne State University, Detroit, Michigan, 48201.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Buren
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.
authors.forename: Kulsoom
authors.initials: K
authors.lastname: Ahmed
authors.affiliation: Karmanos Cancer Center, Detroit, Michigan, 48201.
authors.forename: Gregory
authors.initials: G
authors.lastname: Dyson
authors.affiliation: Department of Veterans Affairs Medical Center, 4646 John R, Detroit, Michigan, 48201.|Karmanos Cancer Center, Detroit, Michigan, 48201.|Department of Internal Medicine, Wayne State University, Detroit, Michigan, 48201.
authors.forename: Adhip P N
authors.initials: AP
authors.lastname: Majumdar
mesh_terms: D000368:Aged; D015415:Biomarkers; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Adenoma; African-Americans; White Americans; cancer stem cells; colorectal cancer; lncRNA; miR-1207-5p; microRNA