Basic—Alimentary TractRNA-Binding Protein Quaking, a Critical Regulator of Colon Epithelial Differentiation and a Suppressor of Colon Cancer
Section snippets
Tissue Sample Collection
Frozen tumor and normal colon mucosa were collected from colectomy specimens from Tangdu Hospital, the University of the Fourth Military Medical University. Tissue was frozen in liquid nitrogen within 30 minutes of resection. Nonneoplastic mucosa from colon was dissected free of muscle and histologically confirmed to be tumor free by frozen section. For cancer tissue, tumor purity of over 70% was confirmed by frozen section for each case before submission for DNA and protein extraction.
Expression Pattern of QKI in Normal Colon and Colon Cancers
To establish the role of QKI in the differentiation of colon epithelium, we first analyzed the expression of QKI in normal colon and colon cancers. Expression levels of QKI were compared among normal gastrointenstinal epithelial cell lines (GES-1 and IEC-6) and cancerous cell lines (HCT116, HT29, SW480, SW620, and Colo205 cells). High expression of QKI in normal GES-1 and IEC-6 cells; median expression in HT29 cells; and low expression in HCT116, SW480, and SW620 cells were observed both at RNA
Discussion
Our study investigated the mechanism how QKI regulates colon epithelial cell differentiation and the role of its aberrant expression in colon cancer evolution. The data demonstrate for the first time that QKI expression, especially QKI6, is widely distributed in normal colon epithelium while absent or very lowly expressed in colon cancer cells because of high methylation of the promoter region. QKI expression in differentiating HT29 cells resulted in sustained accumulation of p27kip1, decreased
Acknowledgments
G.Y., H.F., and J.Z. contributed equally to this work and should be considered as co-first authors.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by Foundation for Excellent Doctoral Level Students of Fourth Military Medical University (200706), National Science Foundation of China (NSF: 30470387; NSF: 30570396; NSF: 30628025), and National Key Basic Research and Development Program 2009CB521704.