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MicroRNA124 Regulated Neurite Elongation by Targeting OSBP

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Abstract

MicroRNA-124 (miR-124), a brain-specific miRNA molecule, has been implicated in stimulating neurite outgrowth and elongation during neuronal differentiation. However, the direct target genes and the mechanisms of miR-124-induced neurite outgrowth are poorly understood. In this study, we demonstrated that miR-124 directly targeted and downregulated the endogenous expression of oxysterol-binding protein (OSBP). A previous study found that the expression of miR-124 increased during brain development. In the present study, we demonstrated that the expression of OSBP decreased during the development of the C57BL/6 mouse cortex, which was negatively correlated with miR-124 expression. OSBP knockdown using specific shRNAs promoted neurite outgrowth and elongation in both Neuro-2a cells and primary cultured mouse cortical neurons. Conversely, OSBP overexpression strongly repressed the neurite elongation-enhancing effect of miR-124 in Neuro-2a cells. Our results suggested that OSBP may be a target and downstream effector of miR-124 for regulating neurite outgrowth and elongation.

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References

  1. Levanon D, Hsieh CL, Francke U, Dawson PA, Ridgway ND, Brown MS, Goldstein JL (1990) cDNA cloning of human oxysterol-binding protein and localization of the gene to human chromosome 11 and mouse chromosome 19. Genomics 7(1):65–74

    Article  CAS  PubMed  Google Scholar 

  2. Taylor FR, Kandutsch AA (1985) Oxysterol binding protein. Chem Phys Lipids 38(1-2):187–194

    Article  CAS  PubMed  Google Scholar 

  3. Taylor FR, Saucier SE, Shown EP, Parish EJ, Kandutsch AA (1984) Correlation between oxysterol binding to a cytosolic binding protein and potency in the repression of hydroxymethylglutaryl coenzyme a reductase. J Biol Chem 259(20):12382–12387

    CAS  PubMed  Google Scholar 

  4. Dawson PA, Van der Westhuyzen DR, Goldstein JL, Brown MS (1989) Purification of oxysterol binding protein from hamster liver cytosol. J Biol Chem 264(15):9046–9052

    CAS  PubMed  Google Scholar 

  5. Olkkonen VM, Li S (2013) Oxysterol-binding proteins: sterol and phosphoinositide sensors coordinating transport, signaling and metabolism. Prog Lipid Res 52(4):529–538. doi:10.1016/j.plipres.2013.06.004

    Article  CAS  PubMed  Google Scholar 

  6. Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303(5654):83–86. doi:10.1126/science.1091903

    Article  CAS  PubMed  Google Scholar 

  7. Lee S, Vasudevan S (2013) Post-transcriptional stimulation of gene expression by microRNAs. Adv Exp Med Biol 768:97–126. doi:10.1007/978-1-4614-5107-5_7

    Article  CAS  PubMed  Google Scholar 

  8. Papagiannakopoulos T, Kosik KS (2009) MicroRNA-124: micromanager of neurogenesis. Cell Stem Cell 4(5):375–376. doi:10.1016/j.stem.2009.04.007

    Article  CAS  PubMed  Google Scholar 

  9. Visvanathan J, Lee S, Lee B, Lee JW, Lee SK (2007) The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev 21(7):744–749. doi:10.1101/gad.1519107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Makeyev EV, Zhang J, Carrasco MA, Maniatis T (2007) The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27(3):435–448. doi:10.1016/j.molcel.2007.07.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Akerblom M, Sachdeva R, Barde I, Verp S, Gentner B, Trono D, Jakobsson J (2012) MicroRNA-124 is a subventricular zone neuronal fate determinant. J of Neurosci Official J Soc Neurosci 32(26):8879–8889. doi:10.1523/jneurosci.0558-12.2012

    Article  Google Scholar 

  12. Cheng LC, Pastrana E, Tavazoie M, Doetsch F (2009) miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci 12(4):399–408. doi:10.1038/nn.2294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yu JY, Chung KH, Deo M, Thompson RC, Turner DL (2008) MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation. Exp Cell Res 314(14):2618–2633. doi:10.1016/j.yexcr.2008.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu Y, Zhang Y, Lin L, Lin F, Li T, Du H, Chen R, Zheng W et al (2013) Effects of bone marrow-derived mesenchymal stem cells on the axonal outgrowth through activation of PI3K/AKT signaling in primary cortical neurons followed oxygen-glucose deprivation injury. PLoS One 8(11):e78514. doi:10.1371/journal.pone.0078514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Smirnova L, Grafe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21(6):1469–1477. doi:10.1111/j.1460-9568.2005.03978.x

    Article  PubMed  Google Scholar 

  16. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5(3):R13. doi:10.1186/gb-2004-5-3-r13

    Article  PubMed  PubMed Central  Google Scholar 

  17. Gu X, Meng S, Liu S, Jia C, Fang Y, Li S, Fu C, Song Q et al (2014) miR-124 represses ROCK1 expression to promote neurite elongation through activation of the PI3K/Akt signal pathway. J Mol Neurosci MN 52(1):156–165. doi:10.1007/s12031-013-0190-6

    Article  CAS  PubMed  Google Scholar 

  18. Franke K, Otto W, Johannes S, Baumgart J, Nitsch R, Schumacher S (2012) miR-124-regulated RhoG reduces neuronal process complexity via ELMO/Dock180/Rac1 and Cdc42 signalling. EMBO J 31(13):2908–2921. doi:10.1038/emboj.2012.130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Beh CT, Cool L, Phillips J, Rine J (2001) Overlapping functions of the yeast oxysterol-binding protein homologues. Genetics 157(3):1117–1140

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Beh CT, Rine J (2004) A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution. J Cell Sci 117(Pt 14):2983–2996. doi:10.1242/jcs.01157

    Article  CAS  PubMed  Google Scholar 

  21. Fiore RS, Bayer VE, Pelech SL, Posada J, Cooper JA, Baraban JM (1993) p42 mitogen-activated protein kinase in brain: prominent localization in neuronal cell bodies and dendrites. Neuroscience 55(2):463–472

    Article  CAS  PubMed  Google Scholar 

  22. Zhu X, Assoian RK (1995) Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation. Mol Biol Cell 6(3):273–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Campbell JS, Wenderoth MP, Hauschka SD, Krebs EG (1995) Differential activation of mitogen-activated protein kinase in response to basic fibroblast growth factor in skeletal muscle cells. Proc Natl Acad Sci U S A 92(3):870–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Perron JC, Bixby JL (1999) Distinct neurite outgrowth signaling pathways converge on ERK activation. Mol Cell Neurosci 13(5):362–378. doi:10.1006/mcne.1999.0753

    Article  CAS  PubMed  Google Scholar 

  25. Wang PY, Weng J, Anderson RG (2005) OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science 307(5714):1472–1476. doi:10.1126/science.1107710

    Article  CAS  PubMed  Google Scholar 

  26. Wu KY, Zippin JH, Huron DR, Kamenetsky M, Hengst U, Buck J, Levin LR, Jaffrey SR (2006) Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones. Nat Neurosci 9(10):1257–1264. doi:10.1038/nn1767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Low VF, Fiorini Z, Fisher L, Jasoni CL (2012) Netrin-1 stimulates developing GnRH neurons to extend neurites to the median eminence in a calcium- dependent manner. PLoS One 7(10):e46999. doi:10.1371/journal.pone.0046999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gomes C, Smith SC, Youssef MN, Zheng JJ, Hagg T, Hetman M (2011) RNA polymerase 1-driven transcription as a mediator of BDNF-induced neurite outgrowth. J Biol Chem 286(6):4357–4363. doi:10.1074/jbc.M110.170134

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81071016), the Program for New Century Excellent Talents in University (NCET-12-0647), the Key Project of Guangdong Province (CXZD1018), and the Program for Changjiang Scholars and the Innovative Research Team in University (IRT1142).

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    Authors and Affiliations

    1. Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China

      Xi Gu, Aili Li, Shuhu Liu, Lifang Lin, Shuang Xu, Peidong Zhang, Shuji Li, Xiaowen Li, Xinhong Zhu & Xuemin Wang

    2. Department of Neurobiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

      Bo Tian

    3. Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China

      Xuemin Wang

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    1. Xi Gu
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    Correspondence to Xuemin Wang.

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    Xi Gu and Aili Li contributed equally to this work.

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    Gu, X., Li, A., Liu, S. et al. MicroRNA124 Regulated Neurite Elongation by Targeting OSBP. Mol Neurobiol 53, 6388–6396 (2016). https://doi.org/10.1007/s12035-015-9540-4

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