Dysregulation of a miR-23b/27b-p53 axis impairs muscle differentiation in humans with type 2 diabetes

Impaired skeletal muscle function is a central feature in the pathophysiology of type 2 diabetes (T2DM). The disease phenotype could be due to immature muscle cell development, which in turn may occur as the result of disturbed microRNA-mediated regulation of muscle differentiation in T2DM. To address this hypothesis, we assessed global miRNA expression during in vitro differentiation of muscle stem cells derived from T2DM patients and healthy controls. We identified the mir-23b/27b cluster to be downregulated in the patients, and further demonstrated that a pro-myogenic effect of these miRNAs occurs through targeting of several genes in the p53 pathway, which was concordantly dysregulated in the muscle cells derived from humans with T2DM. In conclusion, we have identified a novel myogenesis-controlling pathway, the miR-23b/27b-p53 axis, potentially contributing to the sustained multiple muscular dysfunctions in T2DM in humans. Muscle stem cells were isolated from healthy donors (n=8) and donors with type 2 diabetes (n=8). RNA was harvested from proliferating myoblasts, during early myocyte differentiation and late myocyte differentiation.