MiR-146a alleviates inflammatory bowel disease in mice through systematical regulation of multiple genetic networks

Inflammatory bowel disease (IBD) is a multiple-genes-involved chronic disease and current available targeted drugs for IBD only deliver moderate efficacy. Whether there is a single gene that systematically regulates IBD is not yet known. Here we showed that the expression of miR-146a in colon was elevated in Dextran Sulfate Sodium Salt (DSS)-induced IBD mice and patients with IBD. DSS induced dramatic body weight loss and much more rectal bleeding, shorter colon length and colitis in miR-146a knock-out mice than wild type (WT) mice. The miR-146a mimics alleviated DSS-induced symptoms in both DSS-induced miR-146a-/- and WT mice. Further RNA sequencing illustrated that deficiency of miR-146a de-repressed majority of DSS-induced IBD-related genes which cover multiple genetic regulatory networks in IBD, and supplement of miR-146a mimics inhibited expression of many IBD-related genes. DOI 10.3389/fimmu.2024.1366319 Overall design: Experiment1: Bulk RNA of colon profiling data from 3 untreated wild type,3 DSS-treated wild type and 3 DSS-treated miR-146a knock-out mice. Experiment2: Bulk RNA of colon profiling data from 6 (3 females+3 males) DSS+saline treated and 5 (3 females+2males) DSS+miR-146a_mimics treated miR-146a knock-out mice.