title: Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer.
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.
authors.affiliation: Department of Surgery, Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Kanaan
authors.forename: Shesh N
authors.initials: SN
authors.lastname: Rai
authors.forename: M Robert
authors.initials: MR
authors.lastname: Eichenberger
authors.forename: Christopher
authors.initials: C
authors.lastname: Barnes
authors.forename: Amy M
authors.initials: AM
authors.lastname: Dworkin
authors.forename: Clayton
authors.initials: C
authors.lastname: Weller
authors.forename: Eric
authors.initials: E
authors.lastname: Cohen
authors.forename: Henry
authors.initials: H
authors.lastname: Roberts
authors.forename: Bobby
authors.initials: B
authors.lastname: Keskey
authors.forename: Robert E
authors.initials: RE
authors.lastname: Petras
authors.forename: Nigel P S
authors.initials: NP
authors.lastname: Crawford
authors.forename: Susan
authors.initials: S
authors.lastname: Galandiuk
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs