The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells.

Pietro Laneve, Lucia Di Marcotullio, Ubaldo Gioia, Micol E Fiori, Elisabetta Ferretti, Alberto Gulino, Irene Bozzoni, Elisa Caffarelli

Institute of Molecular Biology and Pathology, Consiglio Nazionale delle Ricerche (Italy).

Proceedings of the National Academy of Sciences of the United States of America 2007 May 8

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MicroRNAs (miRNAs) are tiny noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell growth and differentiation. Although the profile of miRNA expression has been defined for many different cellular systems, the elucidation of the regulatory networks in which they are involved is only just emerging. In this work, we identify a crucial role for three neuronal miRNAs (9, 125a, and 125b) in controlling human neuroblastoma cell proliferation. We show that these molecules act in an additive manner by repressing a common target, the truncated isoform of the neurotrophin receptor tropomyosin-related kinase C, and we demonstrate that the down-regulation of this isoform is critical for regulating neuroblastoma cell growth. Consistently with their function, these miRNAs were found to be down-modulated in primary neuroblastoma tumors.

Citation

Pietro Laneve, Lucia Di Marcotullio, Ubaldo Gioia, Micol E Fiori, Elisabetta Ferretti, Alberto Gulino, Irene Bozzoni, Elisa Caffarelli. The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells. Proceedings of the National Academy of Sciences of the United States of America. 2007 May 8;104(19):7957-62