Skip to main content
Log in

Expression profiles of miRNAs during ethanol-induced differentiation of neural stem cells

  • Original Research
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that are gaining recognition as important regulators of gene expression with the capability to modulate cellular events. Although miRNAs are involved in a wide range of activities related to the development and differentiation of cells, evidence for miRNAs that control the ethanol-induced differentiation programs of specific neural cell types has been elusive. In this study, we isolated neural stem cells (NSC) from the forebrains of E14 embryos obtained from pregnant C57/ BL6J mice. We used microarray technology to monitor the expression profiles of miRNAs during ethanol-induced differentiation of NSC. Comparison of the miRNA expression profiles of NSC and differentiated NSC showed that the expression levels of 58 miRNAs changed by twofold after differentiation. Among these differentially expressed miRNAs, we confirmed the downregulation of the two miRNAs miR-21 and miR-338-3p and the upregulation of miR-320 by real time RT-PCR. By computational analysis, we identified 48 target genes that are predicted to be regulated by miR-21, miR-338-3p and miR-320 during differentiation. We found that most of these predicted target genes are related to cellular processes, such as apoptosis, neural differentiation, cell cycle, metabolism, cell signaling and development. Finally, our findings may contribute to a better understanding of miRNA-regulated neural differentiation in response to ethanol.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Temple, S. & Davis, A.A. Isolated rat cortical progenitor cells are maintained in division in vitro by membrane-associated factors. Development 120, 999–1008 (1994).

    CAS  Google Scholar 

  2. Temple, S. The development of neural stem cells. Nature 414, 112–117 (2001).

    Article  CAS  Google Scholar 

  3. Choi, M.R. et al. Ethanol-induced small heat shock protein genes in the differentiation of mouse embryonic neural stem cells. Arch. Toxicol. 85, 293–304 (2011).

    Article  CAS  Google Scholar 

  4. Gong, Z. & Wezeman, F.H. Inhibitory effect of alcohol on osteogenic differentiation in human bone marrowderived mesenchymal stem cells. Alcohol. Clin. Exp. Res. 28, 468–479 (2004).

    Article  Google Scholar 

  5. Jung, K.H. et al. Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol. In Vitro 24, 1696–1704 (2010).

    Article  CAS  Google Scholar 

  6. Li, Z., Lin, H., Zhu, Y., Wang, M. & Luo, J. Disruption of cell cycle kinetics and cyclin-dependent kinase system by ethanol in cultured cerebellar granule progenitors. Brain Res. Dev. Brain Res. 132, 47–58 (2001).

    Article  CAS  Google Scholar 

  7. Crews, F.T., Braun, C.J., Hoplight, B., Switzer, R.C., 3rd & Knapp, D.J. Binge ethanol consumption causes differential brain damage in young adolescent rats compared with adult rats. Alcohol. Clin. Exp. Res. 24, 1712–1723 (2000).

    Article  CAS  Google Scholar 

  8. Livy, D.J., Maier, S.E. & West, J.R. Fetal alcohol exposure and temporal vulnerability: effects of bingelike alcohol exposure on the ventrolateral nucleus of the thalamus. Alcohol. Clin. Exp. Res. 25, 774–780 (2001).

    Article  CAS  Google Scholar 

  9. Hebert, S.S. & De Strooper, B. Alterations of the microRNA network cause neurodegenerative disease. Trends Neurosci. 32, 199–206 (2009).

    Article  CAS  Google Scholar 

  10. Kloosterman, W.P. & Plasterk, R.H. The diverse functions of microRNAs in animal development and disease. Dev. Cell 11, 441–450 (2006).

    Article  CAS  Google Scholar 

  11. Denli, A.M. & Hannon, G.J. RNAi: an ever-growing puzzle. Trends Biochem Sci. 28, 196–201 (2003).

    Article  CAS  Google Scholar 

  12. Bentwich, I. et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat. Genet. 37, 766–770 (2005).

    Article  CAS  Google Scholar 

  13. Croce, C.M. & Calin, G.A. miRNAs, cancer, and stem cell division. Cell 122, 6–7 (2005).

    Article  CAS  Google Scholar 

  14. Krichevsky, A.M., King, K.S., Donahue, C.P., Khrapko, K. & Kosik, K.S. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9, 1274–1281 (2003).

    Article  CAS  Google Scholar 

  15. Conaco, C., Otto, S., Han, J.J. & Mandel, G. Reciprocal actions of REST and a microRNA promote neuronal identity. Proc. Natl. Acad. Sci. USA 103, 2422–2427 (2006).

    Article  CAS  Google Scholar 

  16. Schratt, G.M. et al. A brain-specific microRNA regulates dendritic spine development. Nature 439, 283–289 (2006).

    Article  CAS  Google Scholar 

  17. Miska, E.A. et al. Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol. 5, R68 (2004).

    Article  Google Scholar 

  18. Liu, J. et al. Patterns of gene expression in the frontal cortex discriminate alcoholic from nonalcoholic individuals. Neuropsychopharmacology 31, 1574–1582 (2006).

    Article  CAS  Google Scholar 

  19. Buller, B. et al. MicroRNA-21 protects neurons from ischemic death. FEBS J. 277, 4299–4307 (2010).

    Article  CAS  Google Scholar 

  20. Sathyan, P., Golden, H.B. & Miranda, R.C. Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. J. Neurosci. 27, 8546–8557 (2007).

    Article  CAS  Google Scholar 

  21. Przyborski, S.A., Smith, S. & Wood, A. Transcriptional profiling of neuronal differentiation by human embryonal carcinoma stem cells in vitro. Stem Cells 21, 459–471 (2003).

    Article  CAS  Google Scholar 

  22. Shimazaki, T., Shingo, T. & Weiss, S. The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells. J. Neurosci. 21, 7642–7653 (2001).

    CAS  Google Scholar 

  23. Song, M.R. & Ghosh, A. FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Nat. Neurosci. 7, 229–235 (2004).

    Article  Google Scholar 

  24. Raghunath, M. et al. A novel kinase, AATYK induces and promotes neuronal differentiation in a human neuroblastoma (SH-SY5Y) cell line. Brain Res. Mol. Brain Res. 77, 151–162 (2000).

    Article  CAS  Google Scholar 

  25. Zhao, X. et al. MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 65, 612–626 (2010).

    Article  CAS  Google Scholar 

  26. Saba, R., Goodman, C.D., Huzarewich, R.L., Robertson, C. & Booth, S.A. A miRNA signature of prion induced neurodegeneration. PLoS One 3, e3652 (2008).

    Article  Google Scholar 

  27. Schaar, D.G., Medina, D.J., Moore, D.F., Strair, R.K. & Ting, Y. miR-320 targets transferrin receptor 1 (CD71) and inhibits cell proliferation. Exp. Hematol. 37, 245–255 (2009).

    Article  CAS  Google Scholar 

  28. Broccardo, C. et al. ABCA2 is a marker of neural progenitors and neuronal subsets in the adult rodent brain. J. Neurochem. 97, 345–355 (2006).

    Article  CAS  Google Scholar 

  29. Park, J.H. et al. The characterization of gene expression during mouse neural stem cell differentiation in vitro. Neurosci. Lett. 506, 50–54 (2012).

    Article  CAS  Google Scholar 

  30. John, B. et al. Human MicroRNA targets. PLoS Biol. 2, e363 (2004).

    Article  Google Scholar 

  31. Grimson, A. et al. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell 27, 91–105 (2007).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Kyoung Hwa Jung or Young Gyu Chai.

Additional information

These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, J.H., Halder, D., Choi, M.R. et al. Expression profiles of miRNAs during ethanol-induced differentiation of neural stem cells. BioChip J 6, 73–83 (2012). https://doi.org/10.1007/s13206-012-6110-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-012-6110-y

Keywords

Navigation