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Differential MicroRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer

Authors

  • Ziad Kanaan,

    1. Department of Surgery, Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, Louisville, Kentucky
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  • Shesh N. Rai,

    1. Department of Bioinformatics and Biostatistics, University of Louisville School of Public Health and Information Sciences, Louisville, Kentucky
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  • M. Robert Eichenberger,

    1. Department of Surgery, Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, Louisville, Kentucky
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  • Christopher Barnes,

    1. Department of Bioinformatics and Biostatistics, University of Louisville School of Public Health and Information Sciences, Louisville, Kentucky
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  • Amy M. Dworkin,

    1. National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
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  • Clayton Weller,

    1. Department of Surgery, Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, Louisville, Kentucky
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  • Eric Cohen,

    1. Department of Surgery, Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, Louisville, Kentucky
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  • Henry Roberts,

    1. Department of Surgery, Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, Louisville, Kentucky
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  • Bobby Keskey,

    1. Department of Surgery, Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, Louisville, Kentucky
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  • Robert E. Petras,

    1. Ameripath, Oakwood Village, Ohio
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  • Nigel P.S. Crawford,

    1. National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
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  • Susan Galandiuk

    Corresponding author
    1. Department of Surgery, Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, Louisville, Kentucky
    • Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292
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Errata

This article is corrected by:

  1. Errata: Differential MicroRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer Volume 33, Issue 5, 899, Article first published online: 13 April 2012

  • Communicated by Finlay A. Macrae

Abstract

One of the most serious complications faced by patients with inflammatory bowel disease (IBD) is the potential development of colorectal cancer (CRC). There is a compelling need to enhance the accuracy of cancer screening of IBD patients. MicroRNAs (miRNAs) are small nonprotein-coding RNAs that play important roles in CRC oncogenesis. In this study, we report differential miRNA expression in IBD patients with associated CRC from non-neoplastic tissue to dysplasia and eventually cancer. In addition, we identify and examine the role of dysregulated miRNAs in the TP53 pathway. In our CD patients, six miRNAs were upregulated from non-neoplastic tissue to dysplasia, but downregulated from dysplasia to cancer (miR-122, miR-181a, miR-146b-5p, let-7e, miR-17, miR-143) (P < 0.001). Six differentially expressed miRNAs affected the TP53 pathway (miR-122, miR-214, miR-372, miR-15b, let-7e, miR-17) (P < 0.001). Using two human colon cancer cell lines (HT-29 and HCT-116), E2F1, an upstream regulator of TP53, was downregulated in both cell lines transfected with let-7e (P < 0.05) as well as in HCT-116 cells transfected with miR-17 (P < 0.05). Additionally, cyclin G, a cell-cycle regulator miR-122 target was downregulated in both cell lines (P < 0.05). Unique differentially expressed miRNAs were observed in CD-associated CRC progression. Six of these miRNAs had a tumorigenic effect on the TP53 pathway; the effect of three of which was studied using cell lines. Hum Mutat 33:551–560, 2012. © 2012 Wiley Periodicals, Inc.

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