MiR-375, a microRNA related to diabetes

Abstract

MiR-375 is an important small non-coding RNA that is specifically expressed in islet cells of the pancreas. miR-375 is required for normal pancreatic genesis and influences not only β-cell mass but also α-cell mass. miR-375 is also important to glucose-regulated insulin secretion through the regulation of the expression of Mtpn and Pdk1 genes. When human embryonic stem cells (hESCs) differentiate into endodermal lineages, miR-375 is highly expressed in the definitive endoderm, which suggests that miR-375 may have a distinct role in early development. miR-375 plays an important role in the complex regulatory network of pancreatic development, which could be regulated by pancreatic genes, such as NeuroD1, Ngn3, Pdx1 and Hnf6; additionally, miR-375 regulates genes related to pancreas development, cell growth and proliferation and insulin secretion genes to exert its function. Because of the special role of miR-375, it may be a potential target to treat diabetes. Antagonising miR-375 may enhance the effects of exendin-4 in patients, and controlling the expression of miR-375 could assist mature hESCs-derived β-cells.

Keywords: 3′ UTRs; AIFM1; CADM1; CAV1; CLQBP; Diabetes; EEFLE1; ELAV (embryonic lethal, abnormal vision, drosophila)-like 4; EPAC2; GEF II; GLP-1; HNF1β; HUD; ID3; INSM1; Insulin; MTPN; NGN3; PAX6; PDK1; PDX1; PKA; Pancreas; RAS, dexamethasone-induced 1; RASD1; RGS16; SMARCA2; SOX; SRY (sex determining region Y)-box; SWI/SNF related matrix associated, actin dependent regulator of chromatin, subfamily A, member 2; WHO; World Health Organization; apoptosis-inducing factor, mitochondrion-associated 1; bHLH; basic helix–loop–helix; cAMP; caveolin 1; cell adhesion molecule 1; complement component 1, Q subcomponent binding protein; cyclic adenosine monophosphate; eukaryotic translation elongation factor 1 epsilon 1; exchange protein activated by cyclic AMP 2; glucagon-like peptide-1; guanine nucleotide exchange factor II; hESCs; hepatocyte nuclear factor 1beta; human embryonic stem cells; iPSCs; induced pluripotent stem cells; inhibitor of DNA binding 3; insulinoma-associated protein 1; miR-375; miRNAs; microRNA; myotrophin; neurogenin 3; paired box gene 6; pancreatic and duodenal homeobox 1; protein kinase A; pyruvate dehydrogenase kinase, isozyme 1; regulator of G-protein signaling 16; the 3′ untranslated regions; β-Cells.