miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways

Patients with inflammatory bowel disease are at increased risk for colitis-associated colorectal cancer (CAC). Therefore, controlling intestinal inflammation is a key therapeutic strategy for CAC. MicroRNAs (miRNAs or miRs) are a family of small noncoding RNAs that have the capacity to regulate fundamental biological processes. To date, a number of miRNAs have been identified as critical regulators of inflammation. However, the specific role of miR-26a in colonic inflammation and colitis-associated carcinogenesis is still elusive. Here, we generated mice with miR-26a myeloid-cell-specific overexpression to show that miR-26a suppressed the intestinal inflammatory response in macrophages by decreasing nuclear factor kB (NF-kB)/STAT3 activation and interleukin 6 (IL-6) production. At the molecular level, a number of NF-kB regulators, including TLR3, PTEN, and PKCd, were identified as potential targets of miR-26a. Our results thus identify a novel miRNAmediated mechanism that suppresses carcinogenic inflammation in the colon.