Global MicroRNA Expression Profiling Reveals Differential Expression of Target Genes in 6-Hydroxydopamine-injured MN9D Cells
Tóm tắt
Recent evidence indicates that microRNAs (miRNAs) play a key role in neurodegenerative diseases. However, little is known about how these small RNAs contribute to dopaminergic neuronal apoptosis. Here, we profiled the expression of miRNAs in MN9D cells with and without 6-hydroxydopamine (6-OHDA) treatment by miRCURY™ LNA microRNA arrays. We identified six miRNAs (miR-668-3p, let-7d-3p, miR-3077-3p, miR-665-5p, miR-99b-3p, and miR-323-3p) that were significantly lower and five miRNAs (miR-875, miR-207, miR-425-5p, miR-19b-3p, and miR-338-3p) that were significantly higher after 6-OHDA treatment. Among them, five have been demonstrated to be implicated in neurodegenerative diseases. Consistent with our prediction, the deregulated miRNA’s target mRNAs, such as peroxiredoxin III (Prx III) and Myc, also showed changes in their expression levels. Furthermore, using a dual-luciferase reporter assay, we confirmed that Prx III was a direct target gene of miR-875. Taken together, these findings demonstrate that changes in miRNA expression occur after 6-OHDA treatment and suggest that miRNAs and their predicted targets have a potential role in apoptosis of MN9D cells.
Tài liệu tham khảo
Asikainen, S., Rudgalvyte, M., Heikkinen, L., et al. (2010). Global microRNA expression profiling of Caenorhabditis elegans Parkinson’s disease models. Journal of Molecular Neuroscience, 41(1), 210–218.
Bernstein, A. I., Garrison, S. P., Zambetti, G. P., et al. (2011). 6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death. Molecular Neurodegeneration, 6(1), 2.
Bové, J., Prou, D., Perier, C., et al. (2005). Toxin-induced models of Parkinson’s disease. NeuroRx, 2(3), 484–494.
Brownawell, A. M., & Macara, I. G. (2002). Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins. Journal of Cell Biology, 156(1), 53–64.
Chen, C. X., Huang, S. Y., Zhang, L., et al. (2005). Synaptophysin enhances the neuroprotection of VMAT2 in MPP+-induced toxicity in MN9D cells. Neurobiology of Diseases, 19(3), 419–426.
Choi, H. K., Won, L., Roback, J. D., et al. (1992). Specific modulation of dopamine expression in neuronal hybrid cells by primary cells from different brain regions. Proceedings of the National Academy of Sciences of the United States of America, 89(19), 8943–8947.
Cogswell, J. P., Ward, J., Taylor, I. A., et al. (2008). Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. Journal of Alzheimer’s Disease, 14(1), 27–41.
Delay, C., Calon, F., Mathews, P., et al. (2011). Alzheimer-specific variants in the 3′UTR of Amyloid precursor protein affect microRNA function. Molecular Neurodegeneration, 6, 70.
Dephoure, N., Zhou, C., Villén, J., et al. (2008). A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A, 105(31), 10762–10767.
Ding, Y. M., Jaumotte, J. D., Signore, A. P., et al. (2004). Effects of 6-hydroxydopamine on primary cultures of substantia nigra: Specific damage to dopamine neurons and the impact of glial cell line-derived neurotrophic factor. Journal of Neurochemistry, 89(3), 776–787.
Doxakis, E. (2010). Post-transcriptional regulation of alpha-synuclein expression by mir-7 and mir-153. Journal of Biological Chemistry, 285(17), 12726–12734.
Enciu, A. M., Popescu, B. O., & Gheorghisan-Galateanu, A. (2012). MicroRNAs in brain development and degeneration. Molecular Biology Reports, 39(3), 2243–2252.
Gehrke, S., Imai, Y., Sokol, N., et al. (2010). Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature, 466(7306), 637–641.
Halliwell, B. (2006). Oxidative stress and neurodegeneration: Where are we now? Journal of Neurochemistry, 97(6), 1634–1658.
Hébert, S. S., Horré, K., Nicolaï, L., et al. (2008). Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/beta-secretase expression. Proceedings of the National Academy of Sciences of the United States of America, 105(17), 6415–6420.
Heine, G. F., Horwitz, A. A., Parvin, J. D., et al. (2008). Multiple mechanisms contribute to inhibit transcription in response to DNA damage. Journal of Biological Chemistry, 283(15), 9555–9561.
Jang, H. H., Lee, K. O., Chi, Y. H., et al. (2004). Two enzymes in one; two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell, 117(5), 625–635.
Junn, E., Lee, K. W., Jeong, B. S., et al. (2009). Repression of alpha-synuclein expression and toxicity by microRNA-7. Proceedings of the National Academy of Sciences of the United States of America, 106(31), 13052–13057.
Kim, V. N., Han, J., & Siomi, M. C. (2009). Biogenesis of small RNAs in animals. Nature Reviews Molecular Cell Biology, 10(2), 126–139.
Kim, J., Inoue, K., Ishii, J., et al. (2007). A MicroRNA feedback circuit in midbrain dopamine neurons. Science, 317(5842), 1220–1224.
Klare, J. P., de Orué, Ortiz, & Lucana, D. (2005). Microarray expression profiling identifies early signaling transcripts associated with 6-OHDA-induced dopaminergic cell death. Antioxidants & Redox Signaling, 16(7), 639–648.
Klintworth, H., Newhouse, K., Li, T., et al. (2007). Activation of c-Jun N-terminal protein kinase is a common mechanism underlying paraquat- and rotenone-induced dopaminergic cell apoptosis. Toxicological Sciences, 97(1), 149–162.
Krapfenbauer, K., Engidawork, E., Cairns, N., et al. (2003). Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders. Brain Research, 967(1–2), 152–160.
Kumar, R., Agarwal, A. K., & Seth, P. K. (1995). Free radical-generated neurotoxicity of 6-hydroxydopamine. Journal of Neurochemistry, 64(4), 1703–1707.
Lee, H. P., Kudo, W., Zhu, X., et al. (2011). Early induction of c-Myc is associated with neuronal cell death. Neuroscience Letters, 505(2), 124–127.
Liang, Q., Liou, A. K., Ding, Y., et al. (2004). 6-Hydroxydopamine induces dopaminergic cell degeneration via a caspase-9-mediated apoptotic pathway that is attenuated by caspase-9dn expression. Journal of Neuroscience Research, 77(5), 747–761.
Noelker, C., Schwake, M., Balzer-Geldsetzer, M., et al. (2012). Differentially expressed gene profile in the 6-hydroxy-dopamine-induced cell culture model of Parkinson’s disease. Neuroscience Letters, 507(1), 10–15.
Pothof, J., Verkaik, N. S., van IJcken, W., et al. (2009). MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response. EMBO Journal, 28(14), 2090–2099.
Proietti-De-Santis, L., Drané, P., & Egly, J. M. (2006). Cockayne syndrome B protein regulates the transcriptional program after UV irradiation. EMBO Journal, 25(9), 1915–1923.
Rhee, S. G., Chae, H. Z., & Kim, K. (2005). Peroxiredoxins: A historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radical Biology & Medicine, 38(12), 1543–1552.
Rhee, S. G., Kang, S. W., Chang, T. S., et al. (2001). Peroxiredoxin, a novel family of peroxidases. IUBMB Life, 52(1–2), 35–41.
Rockx, D. A., Mason, R., van Hoffen, A., et al. (2000). UV-induced inhibition of transcription involves repression of transcription initiation and phosphorylation of RNA polymerase II. Proceedings of the National Academy of Sciences of the United States of America, 97(19), 10503–10508.
Saba, R., Goodman, C. D., Huzarewich, R. L., et al. (2008). A miRNA signature of prion induced neurodegeneration. PLoS ONE, 3(11), e3652.
Sampson, V. B., Rong, N. H., Han, J., et al. (2007). MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Research, 67(20), 9762–9770.
Shioya, M., Obayashi, S., Tabunoki, H., et al. (2010). Aberrant microRNA expression in the brains of neurodegenerative diseases: miR-29a decreased in Alzheimer disease brains targets neurone navigator 3. Neuropathology and Applied Neurobiology, 36(4), 320–330.
Sleiman, S. F., Langley, B. C., Basso, M., et al. (2011). Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration. Journal of Neuroscience, 31(18), 6858–6870.
Sonntag, K. C. (2010). MicroRNAs and deregulated gene expression networks in neurodegeneration. Brain Research, 1338, 48–57.
Soto-Otero, R., Méndez-Alvarez, E., Hermida-Ameijeiras, A., et al. (2000). Autoxidation and neurotoxicity of 6-hydroxydopamine in the presence of some antioxidants: Potential implication in relation to the pathogenesis of Parkinson’s disease. Journal of Neurochemistry, 74(4), 1605–1612.
Suzuki, H. I., Yamagata, K., Sugimoto, K., et al. (2009). Modulation of microRNA processing by p53. Nature, 460(7254), 529–533.