MiR-375, a microRNA related to diabetes.

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.

[1]  G. Rutter,et al.  Glucose-stimulated Preproinsulin Gene Expression and Nucleartrans-Location of Pancreatic Duodenum Homeobox-1 Require Activation of Phosphatidylinositol 3-Kinase but Not p38 MAPK/SAPK2* , 2000, The Journal of Biological Chemistry.

[2]  J. Speight,et al.  Patient‐reported outcomes following islet cell or pancreas transplantation (alone or after kidney) in Type 1 diabetes: a systematic review , 2010, Diabetic medicine : a journal of the British Diabetic Association.

[3]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[4]  E. Obberghen,et al.  MicroRNAs in pancreas development , 2012, Diabetes, obesity & metabolism.

[5]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[6]  Gabriel Courties,et al.  MicroRNAs as new player in rheumatoid arthritis. , 2011, Joint, bone, spine : revue du rhumatisme.

[7]  Anton J. Enright,et al.  Genomic analysis of human microRNA transcripts , 2007, Proceedings of the National Academy of Sciences.

[8]  M. Hosoya.  Preparation of pancreatic β-cells from human iPS cells with small molecules , 2012, Islets.

[9]  G. Korbutt,et al.  Generation of Insulin‐Producing Islet‐Like Clusters from Human Embryonic Stem Cells , 2007, Stem cells.

[10]  Eran Hornstein,et al.  The Promoter of the pri-miR-375 Gene Directs Expression Selectively to the Endocrine Pancreas , 2009, PloS one.

[11]  K. Kaestner,et al.  Characterization of Pancreatic Transcription Factor Pdx-1 Binding Sites Using Promoter Microarray and Serial Analysis of Chromatin Occupancy* , 2007, Journal of Biological Chemistry.

[12]  Xiaoqing Tang,et al.  Role of microRNAs in diabetes. , 2008, Biochimica et biophysica acta.

[13]  Ana D. Lopez,et al.  Global gene expression profiling and histochemical analysis of the developing human fetal pancreas , 2008, Diabetologia.

[14]  D. Keller,et al.  Regulation of microRNA-375 by cAMP in pancreatic β-cells. , 2012, Molecular endocrinology.

[15]  G. Daley,et al.  Stage-specific signaling through TGF b family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells , 2022 .

[16]  F. Brunicardi,et al.  Islet Vasculature as a Regulator of Endocrine Pancreas Function , 2007, World Journal of Surgery.

[17]  Rui Wei,et al.  Dynamic expression of microRNAs during the differentiation of human embryonic stem cells into insulin-producing cells. , 2013, Gene.

[18]  H. Deng,et al.  In vitro derivation of functional insulin-producing cells from human embryonic stem cells , 2007, Cell Research.

[19]  J. Eng.  Exendin peptides. , 1992, The Mount Sinai journal of medicine, New York.

[20]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[21]  Gene W. Yeo,et al.  A distinct microRNA signature for definitive endoderm derived from human embryonic stem cells. , 2010, Stem cells and development.

[22]  M. Joglekar,et al.  Expression of islet-specific microRNAs during human pancreatic development. , 2009, Gene expression patterns : GEP.

[23]  Stephen W. Wilson,et al.  MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system , 2007, Genome Biology.

[24]  John Bracht,et al.  MicroRNAs: a developing story. , 2005, Current opinion in genetics & development.

[25]  R. Regazzi.  MicroRNAs and Diabetes , 2013 .

[26]  R. Regazzi,et al.  Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs , 2008, Biological chemistry.

[27]  Wei Jiang,et al.  Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells , 2009, Cell Research.

[28]  H. Horvitz,et al.  MicroRNA Expression in Zebrafish Embryonic Development , 2005, Science.

[29]  E. Miska,et al.  MicroRNA functions in animal development and human disease , 2005, Development.

[30]  M. Wheeler,et al.  Transcription factor expression in the developing human fetal endocrine pancreas , 2008, Diabetologia.

[31]  B. Göke,et al.  Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. , 1993, The Journal of biological chemistry.

[32]  Dongsup Kim,et al.  Expression profiles of miRNAs in human embryonic stem cells during hepatocyte differentiation , 2011, Hepatology research : the official journal of the Japan Society of Hepatology.

[33]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[34]  Mihaela Zavolan,et al.  miR-375 maintains normal pancreatic α- and β-cell mass , 2009, Proceedings of the National Academy of Sciences.

[35]  N. Baroukh,et al.  miR-375 targets PDK 1 and regulates glucose-induced biological responses in pancreatic β-cells , 2008 .

[36]  N. Rajewsky,et al.  A pancreatic islet-specific microRNA regulates insulin secretion , 2004, Nature.

[37]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[38]  E. Kroon,et al.  Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells , 2006, Nature Biotechnology.

[39]  Jennifer Couzin,et al.  MicroRNAs Make Big Impression in Disease After Disease , 2008, Science.

[40]  F. Slack,et al.  Small non-coding RNAs in animal development , 2008, Nature Reviews Molecular Cell Biology.

[41]  Sung-Liang Yu,et al.  Identification of microRNAs expressed highly in pancreatic islet‐like cell clusters differentiated from human embryonic stem cells , 2011, Cell biology international.

[42]  Wigard P Kloosterman,et al.  Targeted Inhibition of miRNA Maturation with Morpholinos Reveals a Role for miR-375 in Pancreatic Islet Development , 2007, PLoS biology.

[43]  John Calvin Reed,et al.  cAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2 , 2003 .

[44]  H. Hahn,et al.  Phases in the early development of the human islet organ. , 1988, Anatomischer Anzeiger.