Effect of depletion of C15ORF48/miR-147 on gene expression in primary colonocytes [colonocytes]

Chronic inflammation is epidemiologically linked to the pathogenesis of gastrointestinal diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, our understanding of the molecular mechanisms controlling gut inflammation remains insufficient, hindering the development of targeted therapies for IBD and CRC. In this study, we uncovered C15ORF48/miR-147 as a novel negative regulator of gut inflammation, operating through the modulation of epithelial cell metabolism. C15ORF48/miR-147 encodes two molecular products, C15ORF48 protein and miR-147-3p microRNA, which are predominantly expressed in intestinal epithelium. C15ORF48/miR-147 ablation leads to gut dysbiosis and exacerbates chemically-induced colitis in mice. C15ORF48 and miR-147-3p work together to suppress colonocyte metabolism and inflammatory responses, and thus bridging mitochondrial metabolism and inflammation.