miR-26a attenuates colitis and colitis-associated cancer by targeting the multiple intestinal inflammatory pathways
Wei Zhang, Xianghui Fu, Jiansheng Xie, Hongming Pan, Weidong Han, Wendong Huang
Abstract
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 κB (NF-κB)/STAT3 activation and interleukin 6 (IL-6) production. At the molecular level, a number of NF-κB regulators, including TLR3, PTEN, and PKCδ, were identified as potential targets of miR-26a. Our results thus identify a novel miRNA-mediated mechanism that suppresses carcinogenic inflammation in the colon. 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 κB (NF-κB)/STAT3 activation and interleukin 6 (IL-6) production. At the molecular level, a number of NF-κB regulators, including TLR3, PTEN, and PKCδ, were identified as potential targets of miR-26a. Our results thus identify a novel miRNA-mediated mechanism that suppresses carcinogenic inflammation in the colon.