miR-24 in diabetes

Diabetes are common diseases threatening health worldwide. Over the past several years it has become clear that alterations in the expression of microRNA (miRNA) genes contribute to the pathogenesis of diabetes [1, 2]. miRNAs are small (~22 nt) regulatory RNA molecules that functionally modulate the activity of specific mRNA targets involving in a wide range of physiologic and pathologic processes [3]. miRNA expression profiling of diabetes has identified signatures associated with diagnosis, progression, prognosis and response to treatment [1]. Here, we focus on one specific miRNA: miR-24, which is involved in both diabetes and diabetic complications. miR-24 is highly conserved in various species and is clustered with miR-23 and miR-27 on human chromosome 9 (miR-24-1) and 19 (miR-24-2). Both miR-24-1 and miR-24-2 generate the same mature product: miR-24. The levels of miR-24 in plasma of diabetes were significantly lower than that in healthy controls [4]. Notably, plasma levels of miR-24 inversely correlated with HbA1c [4]. miR-24 was highly expressed in the lungs, heart, pancreases, and kidneys but poorly expressed in the liver and muscle. Consistent with human observations, miR-24 levels were decreased 2-3 fold in STZ-induced mice and db/db diabetic mice lungs, and 5-fold in db/db mice plasma [4]. In vitro cultured cell line analyses indicate miR-24 is top highly expressed in endothelial cells and beta cells (MIN6 cells) [4, 5]. The expression of miR-24 was decreased response to high glucose culture condition in endothelial cells [4] but was reported upregulated by glucose and palmitate in beta cells [6]. miR-24 was identified targeting multiple 3′UTR sites and genes, directly regulating von Willebrand Factor (VWF) expression and related enzymes or proteins involved in the process of VWF synthesis, maturation and secretion [4]. These lend insight into miR-24-based coordinate regulation of VWF and provide a mechanism for the high plasma VWF levels and thrombotic complications observed with Type 2 diabetes. Thrombotic cardiovascular diseases is the leading cause of mortality among diabetic patients. Of particular interest is miR-24. In the heart, miR-24 has been reported to target BCL2L11 (BIM) and junctophilin-2 in cardiomyocyte, and targeting transcription factor GATA2, p21-activated kinase PAK4 and eNOS in endothelial cells [7]. In the vascular system, miR-24 was found to target chitinase 3-like 1 to limit vascular inflammation and matrix metalloproteinase-14 in macrophage to retard atherosclerotic plaque progression [7]. However, all of these findings are based on in vitro cultured cells and animal studies without an association with …