2024-03-28T09:33:40Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1499392021-12-28T16:20:02Zcom_10261_109com_10261_1col_10261_362
MicroRNAs-10a and -10b contribute to retinoic acid-induced differentiation of neuroblastoma cells and target the alternative splicing regulatory factor SFRS1 (SF2/ASF).
Meseguer, Salvador
Mudduluru, Giridhar
Escamilla Honrubia, Juan Manuel
Allgayer, Heike
Barettino, Domingo
Ministerio de Educación y Ciencia (España)
Ministerio de Ciencia e Innovación (España)
European Association for Cancer Research
Consejo Superior de Investigaciones Científicas (España)
MicroRNA
Neuroblastoma
Neurodifferentiation
Retinoid
RNA Splicing
Translation Control
Retinoic Acid
SFRS1
Alternative splicing
Post-transcriptional
15 páginas, 9 figuras, 3 figuras en material suplementario.
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.
2017-05-18T11:18:35Z
2017-05-18T11:18:35Z
2011-02-11
artículo
Journal of Biological Chemistry 286(6):4150-64 (2011)
0021-9258
http://hdl.handle.net/10261/149939
10.1074/jbc.M110.167817
1083-351X
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/100004437
http://dx.doi.org/10.13039/501100003339
21118818
eng
Publisher's version
http://dx.doi.org/10.1074/jbc.M110.167817
Sí
MEC/SAF2006–00647
MEC/SAF2007–60780
openAccess
American Society for Biochemistry and Molecular Biology