microRNA-181a is involved in insulin-like growth factor-1-mediated regulation of the transcription factor CREB1
Article first published online: 6 AUG 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 126, Issue 6, pages 771–780, September 2013
How to Cite
J. Neurochem. (2013) 126, 771–780.
- Issue published online: 6 SEP 2013
- Article first published online: 6 AUG 2013
- Accepted manuscript online: 19 JUL 2013 05:18AM EST
- Manuscript Accepted: 15 JUL 2013
- Manuscript Revised: 13 JUL 2013
- Manuscript Received: 26 FEB 2013
- The National Natural Science Foundation of China. Grant Number: 30870924
- PC12 cells
microRNAs are a class of small non-coding RNA molecules negatively regulating gene expression at post-transcriptional level in many tissues including the central nervous system. cAMP response element binding protein (CREB) is a key nuclear factor highly expressed in hippocampal neurons on which many signal pathways converge. Recent studies have found that microRNA-181a is rich in mature nerve cells, and bioinformatics analysis shows that the CREB1 mRNA 3′-untranslated region (3′UTR) contains complementary sequence to the miR-181a seed region. In this study, we investigated whether miR-181a is a negative regulator for CREB1 expression in neurons. It was found that the expression of miR-181a was negatively correlated with Insulin-like growth factor-1 (IGF-1) and CREB1 in the Lewis rat hippocampus. miR-181a bound to CREB1 mRNA through a specific binding site in the 3′UTR sequence. The expression of CREB1 in PC12 cells was down-regulated by transfection with a miR-181a mimic and up-regulated by a miR-181a inhibitor. A down-regulated miR-181a and an up-regulated CREB1 were observed in IGF-1-stimulated PC12 cells. And miR-181a inhibited dendritic growth of cultured hippocampus neurons. These suggest that miR-181a is involved in IGF-1-regulated CREB1 expression by targeting its mRNA 3′UTR.
microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and are involved in the central nervous system development. Here, we demonstrate that miR-181a can inhibit the expression of the transcription factor CREB1 by specifically targeting its mRNA 3′UTR and inhibit the development of hippocampus neurons. Repressed expression of miR-181a is involved in IGF-1-mediated up-regulation of CREB1 in vivo and in vitro. These findings indicate that miR-181a could be a potential target for preventing neurodegenerative diseases.