title: MicroRNA-7 regulates the mTOR pathway and proliferation in adult pancreatic β-cells.
abstract: Elucidating the mechanism underlying the poor proliferative capacity of adult pancreatic β-cells is critical to regenerative therapeutic approaches for diabetes. Here, we show that the microRNA (miR)-7/7ab family member miR-7a is enriched in mouse adult pancreatic islets compared with miR-7b. Remarkably, miR-7a targets five components of the mTOR signaling pathway. Further, inhibition of miR-7a activates mTOR signaling and promotes adult β-cell replication in mouse primary islets, which can be reversed by the treatment with a well-known mTOR inhibitor, rapamycin. These data suggest that miR-7 acts as a brake on adult β-cell proliferation. Most importantly, this miR-7-mTOR proliferation axis is conserved in primary human β-cells, implicating miR-7 as a therapeutic target for diabetes.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: You
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiangying
authors.initials: J
authors.lastname: Liu
authors.forename: Chengyang
authors.initials: C
authors.lastname: Liu
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.forename: Doris A
authors.initials: DA
authors.lastname: Stoffers
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D046509:Tissue Culture Techniques; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D035683:MicroRNAs; D058570:TOR Serine-Threonine Kinases; C549242:MIRN7-1 microRNA, human; C549243:MIRN7 microRNA, mouse; C546842:MTOR protein, human; C546843:mTOR protein, mouse