期刊
CELLULAR SIGNALLING
卷 21, 期 12, 页码 1837-1845出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2009.07.019
关键词
MicroRNA; miR-17; miR-17-92; Differentiation; Gene expression; Cancer
类别
资金
- Schizophrenia Research Institute
- NSW Health and the Henderson Foundation
- National Alliance for Research on Schizophrenia and Depression (NARSAD)
- M.C. Ainsworth Fellowship
Whole-genome microRNA and gene expression analyses were used to monitor changes during retinoic acid induced differentiation of neuroblasts in vitro. Interestingly, the entire miR-17 family was over-represented among the down-regulated miRNA. The implications of these changes are considerable, as target gene prediction suggests that the miR-17 family is involved in the regulation of the mitogen-activated protein kinase (MAPK) signaling pathway, synaptic plasticity and other markers of neuronal differentiation. Significantly, many of the target responses predicted by changes in miRNA expression were supported by the observed changes in gene expression. As expected, markers of neuronal differentiation such as anti-apoptotic protein B-cell lymphoma 2 (BCL2), myocyte enhancer factor-2D (MEF2D) and zipper protein kinase (MAP3K12; aka ZPK/MUK/DLK) were each up-regulated in response to differentiation. The expression of these genes was also reduced in response to miR-17 and miR-20a transfection, and more specifically they were also shown to contain functional miRNA recognition elements for members of the miR-17 family by reporter gene assay. This suggests that the miR-17 family have an integral role in fine-tuning the pathways involved in the regulation of neuronal differentiation. (C) 2009 Elsevier Inc. All rights reserved.
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