MicroRNA-29b Regulates Ethanol-induced Neuronal Apoptosis in the Developing Cerebellum through SP1/RAX/PKR Cascade*
- Yuanlin Qi‡,§1,
- Mingfang Zhang‡,¶1,
- Hui Li‡,
- Jacqueline A. Frank‡,
- Lu Dai‖,
- Huijuan Liu‡ and
- Gang Chen‡2
- From the ‡Department of Molecular and Biomedical Pharmacology and
- ‖Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, Kentucky 40536 and
- Departments of §Biochemistry and Molecular Biology and
- ¶Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350004, China
- ↵2 To whom correspondence should be addressed: Dept. of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, 125 Health Sciences Research Bldg., 800 Rose St., Lexington, KY 40536. Tel.: 859-323-0743; Fax: 859-323-1981; E-mail: gangchen6{at}uky.edu.
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↵1 Both authors contributed equally to this work.
Abstract
Neuronal loss is a prominent etiological factor for fetal alcohol spectrum disorders. The cerebellum is one of the areas in the developing central nervous system that is most sensitive to ethanol, especially during the temporal window of ethanol vulnerability. MicroRNAs are small, non-coding RNAs capable of regulating diverse cellular functions including apoptosis. Ethanol exposure has been shown to interfere with the expression of microRNAs. However, the role of microRNAs in ethanol neurotoxicity is still not clear. In the present study, we identified a particular microRNA, miR-29b, as a novel target of ethanol in the developing cerebellar granule neurons. We discovered that ethanol exposure suppressed miR-29b and induced neuronal apoptosis. Overexpression of miR-29b rendered neurons protection against ethanol-induced apoptosis. Furthermore, our data indicated that miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade. More importantly, the expression of miR-29b is developmentally regulated, which may account for, at least partially, the temporal window of ethanol sensitivity in the developing cerebellum.
Footnotes
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↵* This work was supported, in whole or in part, by National Institutes of Health Grant RO1AA020051 (to G. C.).
- Received November 25, 2013.
- Revision received February 7, 2014.
- © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
