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Differential MicroRNA expression tracks neoplastic progression in inflammatory bowel disease‐associated colorectal cancer
Author(s) -
Kanaan Ziad,
Rai Shesh N.,
Eichenberger M. Robert,
Barnes Christopher,
Dworkin Amy M.,
Weller Clayton,
Cohen Eric,
Roberts Henry,
Keskey Bobby,
Petras Robert E.,
Crawford Nigel P.S.,
Galandiuk Susan
Publication year - 2012
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22021
Subject(s) - microrna , biology , cancer research , carcinogenesis , colorectal cancer , cancer , inflammatory bowel disease , dysplasia , downregulation and upregulation , transfection , cyclin d1 , cell cycle , cell culture , disease , medicine , genetics , gene
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.