title: miR-34a regulates mouse neural stem cell differentiation.
abstract: BACKGROUND
  MicroRNAs (miRNAs or miRs) participate in the regulation of several biological processes, including cell differentiation. Recently, miR-34a has been implicated in the differentiation of monocyte-derived dendritic cells, human erythroleukemia cells, and mouse embryonic stem cells. In addition, members of the miR-34 family have been identified as direct p53 targets. However, the function of miR-34a in the control of the differentiation program of specific neural cell types remains largely unknown. Here, we investigated the role of miR-34a in regulating mouse neural stem (NS) cell differentiation.
  
  
  RESULTS
  miR-34a overexpression increased postmitotic neurons and neurite elongation of mouse NS cells, whereas anti-miR-34a had the opposite effect. SIRT1 was identified as a target of miR-34a, which may mediate the effect of miR-34a on neurite elongation. In addition, acetylation of p53 (Lys 379) and p53-DNA binding activity were increased and cell death unchanged after miR-34a overexpression, thus reinforcing the role of p53 during neural differentiation. Interestingly, in conditions where SIRT1 was activated by pharmacologic treatment with resveratrol, miR-34a promoted astrocytic differentiation, through a SIRT1-independent mechanism.
  
  
  CONCLUSIONS
  Our results provide new insight into the molecular mechanisms by which miR-34a modulates neural differentiation, suggesting that miR-34a is required for proper neuronal differentiation, in part, by targeting SIRT1 and modulating p53 activity.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
authors.forename: Márcia M
authors.initials: MM
authors.lastname: Aranha
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Santos
authors.forename: Susana
authors.initials: S
authors.lastname: Solá
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Steer
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
mesh_terms: D000107:Acetylation; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D061251:Primary Cell Culture; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1