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Título: | MicroRNAs-10a and -10b contribute to retinoic acid-induced differentiation of neuroblastoma cells and target the alternative splicing regulatory factor SFRS1 (SF2/ASF). |
Autor: | Meseguer, Salvador CSIC ORCID; Mudduluru, Giridhar; Escamilla Honrubia, Juan Manuel CSIC ORCID; Allgayer, Heike; Barettino, Domingo CSIC | Palabras clave: | MicroRNA Neuroblastoma Neurodifferentiation Retinoid RNA Splicing Translation Control Retinoic Acid SFRS1 Alternative splicing Post-transcriptional |
Fecha de publicación: | 11-feb-2011 | Editor: | American Society for Biochemistry and Molecular Biology | Citación: | Journal of Biological Chemistry 286(6):4150-64 (2011) | Resumen: | MicroRNAs (miRNAs) are an emerging class of non-coding endogenous RNAs involved in multiple cellular processes, including cell differentiation. Treatment with retinoic acid (RA) results in neural differentiation of neuroblastoma cells. We wanted to elucidate whether miRNAs contribute to the gene expression changes induced by RA in neuroblastoma cells and whether miRNA regulation is involved in the transduction of the RA signal. We show here that RA treatment of SH-SY5Y neuroblastoma cells results in profound changes in the expression pattern of miRNAs. Up to 42 different miRNA species significantly changed their expression (26 up-regulated and 16 down-regulated). Among them, the closely related miR-10a and -10b showed the most prominent expression changes. Induction of miR-10a and -10b by RA also could be detected in LA-N-1 neuroblastoma cells. Loss of function experiments demonstrated that miR-10a and -10b are essential mediators of RA-induced neuroblastoma differentiation and of the associated changes in migration, invasion, and in vivo metastasis. In addition, we found that the SR-family splicing factor SFRS1 (SF2/ASF) is a target for miR-10a -and -10b in HeLa and SH-SY5Y neuroblastoma cells. We show here that changes in miR-10a and -10b expression levels may regulate SFRS1-dependent alternative splicing and translational functions. Taken together, our results give support to the idea that miRNA regulation plays a key role in RA-induced neuroblastoma cell differentiation. The discovery of SFRS1 as direct target of miR-10a and -10b supports the emerging functional interaction between two post-transcriptional mechanisms, microRNAs and splicing, in the neuronal differentiation context. | Descripción: | 15 páginas, 9 figuras, 3 figuras en material suplementario. | Versión del editor: | http://dx.doi.org/10.1074/jbc.M110.167817 | URI: | http://hdl.handle.net/10261/149939 | DOI: | 10.1074/jbc.M110.167817 | ISSN: | 0021-9258 | E-ISSN: | 1083-351X |
Aparece en las colecciones: | (IBV) Artículos |
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2011 J Biol Chem 286-04150.pdf | 3,04 MB | Adobe PDF | Visualizar/Abrir |
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