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MiR-21 is an Ngf-modulated microRNA that supports Ngf signaling and regulates neuronal degeneration in PC12 cells.
- Source :
-
Neuromolecular medicine [Neuromolecular Med] 2014 Jun; Vol. 16 (2), pp. 415-30. Date of Electronic Publication: 2014 Feb 04. - Publication Year :
- 2014
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Abstract
- The neurotrophins Ngf, Bdnf, NT-3, NT4-5 have key roles in development, survival, and plasticity of neuronal cells. Their action involves broad gene expression changes at the level of transcription and translation. MicroRNAs (miRs)-small RNA molecules that control gene expression post-transcriptionally-are increasingly implicated in regulating development and plasticity of neural cells. Using PC12 cells as a model system, we show that Ngf modulates changes in expression of a variety of microRNAs, including miRs known to be modulated by neurotrophins-such as the miR-212/132 cluster-and several others, such as miR-21, miR-29c, miR-30c, miR-93, miR-103, miR-207, miR-691, and miR-709. Pathway analysis indicates that Ngf-modulated miRs may regulate many protein components of signaling pathways involved in neuronal development and disease. In particular, we show that miR-21 enhances neurotrophin signaling and controls neuronal differentiation induced by Ngf. Notably, in a situation mimicking neurodegeneration-differentiated neurons deprived of Ngf-this microRNA is able to preserve the neurite network and to support viability of the neurons. These findings uncover a broad role of microRNAs in regulating neurotrophin signaling and suggest that aberrant expression of one or more Ngf-modulated miRs may be involved in neurodegenerative diseases.
- Subjects :
- Animals
Cyclic AMP Response Element-Binding Protein physiology
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
MicroRNAs biosynthesis
MicroRNAs genetics
Neurites ultrastructure
Neurodegenerative Diseases genetics
Neurodegenerative Diseases metabolism
Neurogenesis physiology
Neurons metabolism
PC12 Cells
RNA, Neoplasm biosynthesis
RNA, Neoplasm genetics
Rats
Real-Time Polymerase Chain Reaction
Signal Transduction genetics
Signal Transduction physiology
MicroRNAs physiology
Nerve Growth Factor physiology
Neurons pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1174
- Volume :
- 16
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuromolecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24492999
- Full Text :
- https://doi.org/10.1007/s12017-014-8292-z