MiR-21 is an Ngf-modulated MicroRNA That supports Ngf signaling and regulates neuronal degeneration in PC12 cells

Enrica Montalban, Nicola Mattugini, Roberta Ciarapica, Claudia Provenzano, Mauro Savino, Fiorella Scagnoli, Gianluca Prosperini, Claudia Carissimi, Valerio Fulci, Carmela Matrone, Pietro Calissano, Sergio Nasi

Research output: Contribution to journalArticlepeer-review

Abstract

The neurotrophins Ngf, Bdnf, NT-3, NT4-5 have key roles in development, survival, and plasticity of neuronal cells. Their action involves broad gene expression changes at the level of transcription and translation. MicroRNAs (miRs) - small RNA molecules that control gene expression post-transcriptionally - are increasingly implicated in regulating development and plasticity of neural cells. Using PC12 cells as a model system, we show that Ngf modulates changes in expression of a variety of microRNAs, including miRs known to be modulated by neurotrophins - such as the miR-212/132 cluster - and several others, such as miR-21, miR-29c, miR-30c, miR-93, miR-103, miR-207, miR-691, and miR-709. Pathway analysis indicates that Ngf-modulated miRs may regulate many protein components of signaling pathways involved in neuronal development and disease. In particular, we show that miR-21 enhances neurotrophin signaling and controls neuronal differentiation induced by Ngf. Notably, in a situation mimicking neurodegeneration - differentiated neurons deprived of Ngf - this microRNA is able to preserve the neurite network and to support viability of the neurons. These findings uncover a broad role of microRNAs in regulating neurotrophin signaling and suggest that aberrant expression of one or more Ngf-modulated miRs may be involved in neurodegenerative diseases.

Original languageEnglish
Pages (from-to)415-430
Number of pages16
JournalNeuroMolecular Medicine
Volume16
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • Differentiation
  • Gene expression
  • MicroRNA
  • Neurodegeneration
  • Neurotrophins
  • Signaling

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Neurology
  • Medicine(all)

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