Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells
17 páginas, 9 figuras, 5 tablas.
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BioMed Central
2010-12-10
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| Online Access: | http://hdl.handle.net/10261/33482 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100002809 http://dx.doi.org/10.13039/501100004837 |
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dig-ibe-es-10261-334822021-12-28T16:27:32Z Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells Guidi, Mónica Muiños-Gimeno, Margarita Kagerbauer, Birgit Martí, Eulàlia Estivill, Xavier Espinosa-Parrilla, Yolanda European Commission Instituto de Salud Carlos III Instituto de Salud Carlos III Generalitat de Catalunya Ministerio de Ciencia e Innovación (España) Ministerio de Educación y Ciencia (España) Ministerio de Sanidad y Consumo (España) 17 páginas, 9 figuras, 5 tablas. [Background]: Neurotrophins and their receptors are key molecules in the regulation of neuronal differentiation and survival. They mediate the survival of neurons during development and adulthood and are implicated in synaptic plasticity. The human neurotrophin-3 receptor gene NTRK3 yields two major isoforms, a full-length kinase-active form and a truncated non-catalytic form, which activates a specific pathway affecting membrane remodeling and cytoskeletal reorganization. The two variants present non-overlapping 3'UTRs, indicating that they might be differentially regulated at the post-transcriptional level. Here, we provide evidence that the two isoforms of NTRK3 are targeted by different sets of microRNAs, small non-coding RNAs that play an important regulatory role in the nervous system. [Results]: We identify one microRNA (miR-151-3p) that represses the full-length isoform of NTRK3 and four microRNAs (miR-128, miR-485-3p, miR-765 and miR-768-5p) that repress the truncated isoform. In particular, we show that the overexpression of miR-128 - a brain enriched miRNA - causes morphological changes in SH-SY5Y neuroblastoma cells similar to those observed using an siRNA specifically directed against truncated NTRK3, as well as a significant increase in cell number. Accordingly, transcriptome analysis of cells transfected with miR-128 revealed an alteration of the expression of genes implicated in cytoskeletal organization as well as genes involved in apoptosis, cell survival and proliferation, including the anti-apoptotic factor BCL2. [Conclusions]: Our results show that the regulation of NTRK3 by microRNAs is isoform-specific and suggest that neurotrophin-mediated processes are strongly linked to microRNA-dependent mechanisms. In addition, these findings open new perspectives for the study of the physiological role of miR-128 and its possible involvement in cell death/survival processes. This work was supported by the European Union Sixth Framework Programme Integrated Project SIROCCO (Grant LSHG-CT- 2006-037900), the “Instituto Carlos III and Fondo de Investigaciones Sanitarias” (CIBER-CB06/02/0058, FIS/ISCIII:P1052565, ISCIII:GO3/184), the “Departament d’Universitats Innovació i Empresa, Generalitat de Catalunya” (2005SGR00008) and the Spanish Ministry of Science and Innovation (MICINN-SAF2008-00357). M.G. was funded by the Spanish Ministry of Education and Science (FPU fellowship). M.M.G. is a recipient of a FIS fellowship (FI05/0006). Y.E.P. was supported by the “Ramón y Cajal” Program (Spanish Ministry of Science and Innovation). E.M. is supported by the Spanish Ministry of Health. Peer reviewed 2011-03-17T10:27:01Z 2011-03-17T10:27:01Z 2010-12-10 artículo http://purl.org/coar/resource_type/c_6501 BMC Evolutionary Biology 11: 95 (2010) 1471-2148 http://hdl.handle.net/10261/33482 10.1186/1471-2199-11-95 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100002809 http://dx.doi.org/10.13039/501100004837 21143953 en Publisher’s version http://dx.doi.org/10.1186/1471-2199-11-95 Sí open BioMed Central |
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17 páginas, 9 figuras, 5 tablas. |
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European Commission |
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European Commission Guidi, Mónica Muiños-Gimeno, Margarita Kagerbauer, Birgit Martí, Eulàlia Estivill, Xavier Espinosa-Parrilla, Yolanda |
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Guidi, Mónica Muiños-Gimeno, Margarita Kagerbauer, Birgit Martí, Eulàlia Estivill, Xavier Espinosa-Parrilla, Yolanda |
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Guidi, Mónica Muiños-Gimeno, Margarita Kagerbauer, Birgit Martí, Eulàlia Estivill, Xavier Espinosa-Parrilla, Yolanda Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells |
| author_sort |
Guidi, Mónica |
| title |
Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells |
| title_short |
Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells |
| title_full |
Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells |
| title_fullStr |
Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells |
| title_full_unstemmed |
Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells |
| title_sort |
overexpression of mir-128 specifically inhibits the truncated isoform of ntrk3 and upregulates bcl2 in sh-sy5y neuroblastoma cells |
| publisher |
BioMed Central |
| publishDate |
2010-12-10 |
| url |
http://hdl.handle.net/10261/33482 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100002809 http://dx.doi.org/10.13039/501100004837 |
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