title: MicroRNA-124 regulates neuronal differentiation of mesenchymal stem cells by targeting Sp1 mRNA.
abstract: MicroRNAs play an important role in neuronal development and function. miR-124 is the most abundantly expressed miRNA in the nervous system. Several different mRNA targets have been proposed for miR-124, but the precise function of endogenous miR-124 and its mRNA targets remain to be further elucidated. Specificity protein 1 (Sp1) is a transcription factor that plays key roles in many cell processes including cell cycle. However, this transcription factor is nearly absent in differentiated neurons and a remarkable suppression of Sp1 expression was shown after neurogenesis. Since miR-124 is expressed abundantly in neurons and because Sp1 levels decrease during neurogenesis, it is possible that miR-124 could regulate the expression of Sp1 during neuronal development. Therefore, the aim of the present study was to evaluate the putative targeting of Sp1 by miR-124. Overexpression of miR-124 using a plasmid coding for pri-miR-124 in HEK293 cells decreased the expression of Sp1 mRNA. The results of dual-luciferase reporter assay demonstrated that miR-124 directly targeted the 3'-untranslated regions of Sp1 mRNA. To evaluate whether Sp1 expression was regulated by miR-124 during the process of neuronal differentiation, Adipose-derived mesenchymal stem cells (A-MSCs) were differentiated into neuron-like cells. The results of qPCR analysis showed that with the gradual increase of miR-124 expression during neurogenesis, the expression of Sp1 mRNA decreased accordingly. In summary, this study demonstrated for the first time that miR-124 is able to suppress Sp1 expression, which in turn affected the neuronal differentiation of mesenchymal stem cells.
authors.affiliation: Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Mondanizadeh
authors.forename: Ehsan
authors.initials: E
authors.lastname: Arefian
authors.forename: Ghasem
authors.initials: G
authors.lastname: Mosayebi
authors.forename: Massoud
authors.initials: M
authors.lastname: Saidijam
authors.forename: Behzad
authors.initials: B
authors.lastname: Khansarinejad
authors.forename: Seyed Mahmoud
authors.initials: SM
authors.lastname: Hashemi
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000235:genetics*
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor
keywords: CELL DIFFERENTIATION; MicroRNAs; NEUROGENESIS; SPECIFIC PROTEIN 1; miR-124