miR-146a Influences Energy Metabolism, Cell Differentiation and Innate Immunity

Abstract

MicroRNAs play key regulatory roles in many different biological processes, including development, differentiation, homeostasis and inflammation. The latest version of miRBase lists over 1100 distinct microRNA sequences in mice and over 1800 in humans. One pair of mature microRNAs whose 3’ regions differ by only 2 nucleotides, miR-146a and miR- 146b, is involved in metabolism, differentiation and immunity. NF-κB directly induces miR-146a, while both miR-146a and miR-146b target NF-κB pathway components interleukin-1 receptor-associated kinase 1 (Irak1) and tumor necrosis factor receptor-associated factor-6 (Traf6) for repression. Inhibition of miR-146a increases glucose-stimulated insulin secretion and promotes differentiation of mouse spermatogonia. Muscle-specific inactivation of mediator complex subunit 1 (Med1), another miR-146a target, enhances insulin sensitivity and improves glucose tolerance in mice. This review highlights the role of miR-146a in metabolic regulation, hematopoietic and spermatogenic differentiation, and induction of the immune response.