Role of cancer stem cells in racial disparity in colorectal cancer
| Autor: | Yingjie Yu, Farhan Murshed, Eric Van Buren, Mohammad R. Anees, Edi Levi, Lulu Farhana, Adhip P.N. Majumdar, Stephanie Judd, Timothy Hadden, Gregory Dyson, Pratima Nangia-Makker, Fadi Antaki, Kulsoom Ahmed |
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| Rok vydání: | 2016 |
| Předmět: |
Male
cancer stem cells 0301 basic medicine Cancer Research Pathology Colorectal cancer lncRNA 0302 clinical medicine Immunophenotyping Ethnicity Original Research Cancer Biology microRNA biology miR‐1207‐5p Middle Aged 3. Good health PVT1 Phenotype Oncology 030220 oncology & carcinogenesis Neoplastic Stem Cells Female Colorectal Neoplasms Adenoma medicine.medical_specialty colorectal cancer 03 medical and health sciences Cancer stem cell Cell Line Tumor medicine Humans Radiology Nuclear Medicine and imaging Epithelial–mesenchymal transition Aged Gene Expression Profiling African‐Americans CD44 White Americans Reproducibility of Results Cancer medicine.disease digestive system diseases MicroRNAs 030104 developmental biology biology.protein Cancer research Biomarkers |
| Zdroj: | Cancer Medicine |
| ISSN: | 2045-7634 |
| DOI: | 10.1002/cam4.690 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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