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Journal article
MicroRNAs 21 and 199a-3p Regulate Axon Growth Potential through Modulation of Pten and mTor mRNAs
eNeuro, v 8(4)
01 Jul 2021
PMID: 34326064
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Increased mTOR activity has been shown to enhance regeneration of injured axons by increasing neuronal protein synthesis, while PTEN signaling can block mTOR activity to attenuate protein synthesis. MicroRNAs (miRs) have been implicated in regulation of PTEN and mTOR expression, and previous work in spinal cord showed an increase in miR-199a-3p after spinal cord injury (SCI) and increase in miR-21 in SCI animals that had undergone exercise. Pten mRNA is a target for miR-21 and miR-199a-3p is predicted to target mTor mRNA. Here, we show that miR-21 and miR-199a-3p are expressed in adult dorsal root ganglion (DRG) neurons, and we used culture preparations to test functions of the rat miRs in adult DRG and embryonic cortical neurons. miR-21 increases and miR-199a-3p decreases in DRG neurons after in vivo axotomy. In both the adult DRG and embryonic cortical neurons, miR-21 promotes and miR-199a-3p attenuates neurite growth. miR-21 directly bound to Pten mRNA and miR-21 overexpression decreased Pten mRNA levels. Conversely, miR-199a-3p directly bound to mTor mRNA and miR-199a-3p overexpression decreased mTor mRNA levels. Overexpressing miR-21 increased both overall and intra-axonal protein synthesis in cultured DRGs, while miR-199a-3p overexpression decreased this protein synthesis. The axon growth phenotypes seen with miR-21 and miR-199a-3p overexpression were reversed by co-transfecting PTEN and mTOR cDNA expression constructs with the predicted 39 untranslated region (UTR) miR target sequences deleted. Taken together, these studies indicate that injury-induced alterations in miR-21 and miR-199a-3p expression can alter axon growth capacity by changing overall and intra-axonal protein synthesis through regulation of the PTEN/mTOR pathway.
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Details
- Title
- MicroRNAs 21 and 199a-3p Regulate Axon Growth Potential through Modulation of Pten and mTor mRNAs
- Creators
- Amar N. Kar - University of South CarolinaSeung-Joon Lee - University of South CarolinaPabitra K. Sahoo - University of South CarolinaElizabeth Thames - University of South CarolinaSoonmoon Yoo - Alfred I. duPont Hospital for ChildrenJohn D. Houle - Drexel UniversityJeffery L. Twiss - University of South Carolina
- Publication Details
- eNeuro, v 8(4)
- Publisher
- Soc Neuroscience
- Number of pages
- 16
- Grant note
- 2019PD-02 / South Carolina Spinal Cord Injury Research Fund Grant P01NS055976; R21-NS099959; R01-NS117821 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000728395700004
- Scopus ID
- 2-s2.0-85112197018
- Other Identifier
- 991019169661104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences