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MicroRNA‐124 Regulates Neuronal Differentiation of Mesenchymal Stem Cells by Targeting Sp1 mRNA
Author(s) -
Mondanizadeh Mahdieh,
Arefian Ehsan,
Mosayebi Ghasem,
Saidijam Massoud,
Khansarinejad Behzad,
Hashemi Seyed Mahmoud
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25045
Subject(s) - neurogenesis , microrna , biology , microbiology and biotechnology , sp1 transcription factor , transcription factor , messenger rna , cellular differentiation , mesenchymal stem cell , gene expression , promoter , genetics , gene
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. J. Cell. Biochem. 116: 943–953, 2015. © 2015 Wiley Periodicals, Inc.