title: miR-26a Mediates Adipogenesis of Amniotic Fluid Mesenchymal Stem/Stromal Cells via PTEN, Cyclin E1, and CDK6.
abstract: Recent findings indicate that microRNAs (miRNAs) are critical for the regulatory network of adipogenesis in human mesenchymal stem/stromal cells (MSCs). Fetal MSCs derived from amniotic fluid (AF-MSCs) represent a population of multipotent stem cells characterized by a wide range of differentiation properties that can be applied in cell-based therapies. In this study, miRNA microarray analysis was performed to assess miRNA expression in terminal differentiated AF-MSCs into adipocyte-like cells (AL cells). MiR-26a was identified in high expression levels in AL cells indicating a critical role in the process of adipogenesis. Overexpression of miR-26a in AF-MSCs led to significant induction of their adipogenic differentiation properties that were altered after miR-26a inhibition. We have demonstrated that miR-26a regulates adipogenesis through direct inhibition of PTEN, which in turn promotes activation of Akt pathway. Also, miR-26a modulates cell cycle during adipogenesis by interacting with Cyclin E1 and CDK6. These results point to the regulatory role of miR-26a and its target genes PTEN, Cyclin E1, and CDK6 in adipogenic differentiation of AF-MSCs, providing a basis for understanding the mechanisms of fat cell development and obesity.
authors.affiliation: 1 Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens , Athens, Greece .|2 Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens (BRFAA) , Athens, Greece .
authors.forename: Ourania
authors.initials: O
authors.lastname: Trohatou
authors.affiliation: 1 Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens , Athens, Greece .|2 Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens (BRFAA) , Athens, Greece .
authors.forename: Dimitra
authors.initials: D
authors.lastname: Zagoura
authors.affiliation: 2 Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens (BRFAA) , Athens, Greece .
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Orfanos
authors.affiliation: 3 First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens , Athens, Greece .
authors.forename: Kalliopi I
authors.initials: KI
authors.lastname: Pappa
authors.affiliation: 1 Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens , Athens, Greece .
authors.forename: Evangelos
authors.initials: E
authors.lastname: Marinos
authors.affiliation: 1 Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens , Athens, Greece .|2 Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens (BRFAA) , Athens, Greece .
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Anagnou
authors.affiliation: 1 Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens , Athens, Greece .|2 Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens (BRFAA) , Athens, Greece .
authors.forename: Maria G
authors.initials: MG
authors.lastname: Roubelakis
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000166:cytology; D000653:Amniotic Fluid / Q000378:metabolism; D002478:Cells, Cultured; D019927:Cyclin E / Q000378:metabolism*; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D039902:Multipotent Stem Cells / Q000166:cytology*; D015513:Oncogene Proteins / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000378:metabolism*
chemical_list: D019927:Cyclin E; D051361:Cyclin-Dependent Kinase 6; D035683:MicroRNAs; D015513:Oncogene Proteins; D051059:PTEN Phosphohydrolase; C475820:CCNE1 protein, human; C528163:MIRN26 microRNA, human; C495911:CDK6 protein, human; C494929:PTEN protein, human
keywords: AF-MSCs; Akt; MSCs; adipogenesis; differentiation; miR-26a