Overexpression of miR-595 and miR-1246 in the sera of patients with active forms of inflammatory bowel disease.

BACKGROUND: MicroRNAs (miRNAs) are dysregulated in the inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), which arise due to dysfunctional host-microbe interactions and impairment of the barrier function of the intestine. Here, we sought to determine whether circulating miRNAs are biomarkers of active colonic CD and UC and can provide insights into disease pathogenesis. Comparison was made with serum miRNAs in patients with rheumatoid arthritis (RA).

METHODS: Total serum RNA from patients with colonic CD, UC, and RA, and normal healthy adults was screened for disease-associated miRNAs by microarray analysis, with subsequent validation by quantitative reverse-transcription polymerase chain reaction. MiRNA targets were identified by luciferase reporter assays.

RESULTS: MiR-595 and miR-1246 were significantly upregulated in the sera of active colonic CD, UC, and RA patients, compared with healthy subjects; and in active colonic CD and UC compared with inactive disease. Luciferase reporter assays indicated that miR-595 inhibits the expression of neural cell adhesion molecule-1 and fibroblast growth factor receptor 2.

CONCLUSIONS: Serum miR-595 and miR-1246 are biomarkers of active CD, UC, and RA. These findings gain significance from reports that miR-595 impairs epithelial tight junctions, whereas miR-1246 indirectly activates the proinflammatory nuclear factor of activated T cells. miR-595 targets the cell adhesion molecule neural cell adhesion molecule-1, and fibroblast growth factor receptor 2, which plays a key role in the differentiation, protection, and repair of colonic epithelium, and maintenance of tight junctions. miR-595 and miR-1246 warrant testing as potential targets for therapeutic intervention in the treatment of inflammatory bowel disease.