5-aminosalicylic acid inhibits the expression of oncomiRs and pro-inflammatory microRNAs: an in vitro study.

Abstract

5-aminosalicylic acid (5-ASA) is commonly used as the first-line treatment for ulcerative colitis (UC). In this study, we show that the mechanism responsible for the protective effect of 5-ASA is associated with the modulation of non-coding microRNA molecule (miRNA) expression. Stimulation of human intestinal epithelial cells (Caco-2) with 1000 μM of 5-ASA suppressed the levels of miR-125b, miR-150, miR-155, miR-346 and miR-506, which are known to be involved in the regulation of colitis and/or colorectal cancer in patients with inflammatory bowel disease. The 5-ASA-induced inhibitions of these miRNAs were associated with significant inductions of their target genes such as vitamin D receptor (VDR), suppressor of cytokine signaling (SOCS1), Forkhead box O (FOXO3a) and DNA methyltransferase 1 (DNMT1). The relationships between the selected miRNAs and their target genes were further confirmed in Caco-2 cells transfected of with specific miRNA inhibitors or miRNA mimics. Moreover, we showed that 5-ASA has the potential to hinder miR-155 expression induced by the transfection of miR-155 mimic into Caco-2 cells. These findings underline the anti-inflammatory and chemoprotective effects of 5-ASA treatment.