Apoptosis-associated microRNAs are modulated in mouse, rat and human neural differentiation

Márcia M. Aranha, Daniela M. Santos, Joana M. Xavier, Walter C. Low, Clifford J. Steer, Susana Solá, Cecília M P Rodrigues

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67 Scopus citations

Abstract

Background: MicroRNAs (miRs or miRNAs) regulate several biological processes in the cell. However, evidence for miRNAs that control the differentiation program of specific neural cell types has been elusive. Recently, we have shown that apoptosis-associated factors, such as p53 and caspases participate in the differentiation process of mouse neural stem (NS) cells. To identify apoptosis-associated miRNAs that might play a role in neuronal development, we performed global miRNA expression profiling experiments in NS cells. Next, we characterized the expression of proapoptotic miRNAs, including miR-16, let-7a and miR-34a in distinct models of neural differentiation, including mouse embryonic stem cells, PC12 and NT2N cells. In addition, the expression of antiapoptotic miR-19a and 20a was also evaluated.Results: The expression of miR-16, let-7a and miR-34a was consistently upregulated in neural differentiation models. In contrast, expression of miR-19a and miR-20a was downregulated in mouse NS cell differentiation. Importantly, differential expression of specific apoptosis-related miRNAs was not associated with increased cell death. Overexpression of miR-34a increased the proportion of postmitotic neurons of mouse NS cells.Conclusions: In conclusion, the identification of miR-16, let-7a and miR-34a, whose expression patterns are conserved in mouse, rat and human neural differentiation, implicates these specific miRNAs in mammalian neuronal development. The results provide new insights into the regulation of neuronal differentiation by apoptosis-associated miRNAs.

Original languageEnglish (US)
Article number514
JournalBMC Genomics
Volume11
Issue number1
DOIs
StatePublished - Sep 24 2010

Bibliographical note

Funding Information:
We would like to acknowledge Yan Zeng (University of Minnesota Medical School, Minneapolis, Minnesota, USA) for miRNA expression profiling, and Rui Castro (iMed.UL, Lisbon, Portugal) for microarray data analysis. The authors thank Ricardo Viana and Inês Milagre (iMed.UL, Lisbon, Portugal) for providing PC12 and NT2N cell cultures, and Domingos Henrique (IMM, Lisbon, Portugal) for ES cell lines. This work was supported by grant PTDC/ BIA-BCM/67922/2006 from Fundação para a Ciência e a Tecnologia (FCT), Lisbon, Portugal. MM Aranha and DM Santos are recipients of PhD fellowships from FCT, Portugal (SFRH/BD/28429/2006 and SFRH/BD/42008/ 2007, respectively).

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