Target gene repression mediated by miRNAs miR-181c and miR-9 both of which are down-regulated by amyloid-β

J Mol Neurosci. 2012 Feb;46(2):324-35. doi: 10.1007/s12031-011-9587-2. Epub 2011 Jul 1.

Abstract

MicroRNAs (miRNAs) are small non-coding RNA regulators of protein synthesis that are essential for normal brain development and function. Their profiles are significantly altered in neurodegenerative diseases such as Alzheimer's disease (AD) that is characterized by amyloid-β (Aβ) and tau deposition in brain. How deregulated miRNAs contribute to AD is not understood, as their dysfunction could be both a cause and a consequence of disease. To address this question we had previously profiled miRNAs in models of AD. This identified miR-9 and -181c as being down-regulated by Aβ in hippocampal cultures. Interestingly, there was a remarkable overlap with those miRNAs that are deregulated in Aβ-depositing APP23 transgenic mice and in human AD tissue. While the Aβ precursor protein APP itself is a target of miRNA regulation, the challenge resides in identifying further targets. Here, we expand the repertoire of miRNA target genes by identifying the 3' untranslated regions (3' UTRs) of TGFBI, TRIM2, SIRT1 and BTBD3 as being repressed by miR-9 and -181c, either alone or in combination. Taken together, our study identifies putative target genes of miRNAs miR-9 and 181c, which may function in brain homeostasis and disease pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / physiology*
  • Animals
  • Brain / metabolism
  • DNA, Recombinant / genetics
  • Down-Regulation
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Mice
  • MicroRNAs / physiology*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Sirtuin 1 / biosynthesis
  • Sirtuin 1 / genetics*
  • Transcription, Genetic
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics*

Substances

  • 3' Untranslated Regions
  • Amyloid beta-Peptides
  • BTBD3 protein, human
  • DNA, Recombinant
  • Extracellular Matrix Proteins
  • MIRN92 microRNA, human
  • MIrn181 microRNA, human
  • MicroRNAs
  • Narf protein, human
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Transforming Growth Factor beta
  • betaIG-H3 protein
  • SIRT1 protein, human
  • Sirtuin 1