Identification of microRNA transcriptome reveals that miR-100 is involved in the renewal of porcine intestinal epithelial cells.

Abstract

MicroRNAs play important roles in various cellular processes, including differentiation, proliferation and survival. Using a pig model, this study sought to identify the miRNAs responsible for crypt-villus axis renewal of the small intestinal epithelium. Compared to the villus upper cells, there were 15 up-regulated and 41 down-regulated miRNAs in the crypt cells of the jejunum. Notably, we found that miR-100 was expressed more in the villus upper cells than in the crypt cells, suggesting an effect on intestinal epithelium differentiation. Overexpression of miR-100 increased the activity of alkaline phosphatase, confirming that miR-100 promoted IPEC-J2 cell differentiation. MiR-100 can inhibit cell proliferation as evidenced by CCK-8 and cell cycle assay results. We also showed that miR-100 significantly inhibited the migration of IPEC-J2 cells and promoted cell apoptosis through caspase-3-dependent cleavage of Bcl-2. Furthermore, FGFR3 was identified as a potential target of miR-100 by bioinformatics analysis. We confirmed that overexpression of miR-100 suppressed FGFR3 expression in IPEC-J2 cells by directly targeting the FGFR3 3'-UTR. This is the first report of miRNAs acting on the renewal of the intestinal crypt-villus axis. Our results also showed that miR-100 promotes the differentiation and apoptosis, and inhibits the proliferation and migration of enterocytes of pigs.