Up-Regulation of MicroRNAs in Brain of Human Alcoholics

Authors

  • Joanne M. Lewohl,

    1. From the School of Medical Science & Griffith Health Institute (JML), Griffith University, Southport, Australia; Waggoner Center for Alcohol and Addiction Research (YON, GRT, RAH, RDM), University of Texas at Austin, Austin, Texas; and School of Molecular and Microbial Sciences (PRD), University of Queensland, St. Lucia, Australia.
    Search for more papers by this author
  • Yury O. Nunez,

    1. From the School of Medical Science & Griffith Health Institute (JML), Griffith University, Southport, Australia; Waggoner Center for Alcohol and Addiction Research (YON, GRT, RAH, RDM), University of Texas at Austin, Austin, Texas; and School of Molecular and Microbial Sciences (PRD), University of Queensland, St. Lucia, Australia.
    Search for more papers by this author
  • Peter R. Dodd,

    1. From the School of Medical Science & Griffith Health Institute (JML), Griffith University, Southport, Australia; Waggoner Center for Alcohol and Addiction Research (YON, GRT, RAH, RDM), University of Texas at Austin, Austin, Texas; and School of Molecular and Microbial Sciences (PRD), University of Queensland, St. Lucia, Australia.
    Search for more papers by this author
  • Gayatri R. Tiwari,

    1. From the School of Medical Science & Griffith Health Institute (JML), Griffith University, Southport, Australia; Waggoner Center for Alcohol and Addiction Research (YON, GRT, RAH, RDM), University of Texas at Austin, Austin, Texas; and School of Molecular and Microbial Sciences (PRD), University of Queensland, St. Lucia, Australia.
    Search for more papers by this author
  • R. Adron Harris,

    1. From the School of Medical Science & Griffith Health Institute (JML), Griffith University, Southport, Australia; Waggoner Center for Alcohol and Addiction Research (YON, GRT, RAH, RDM), University of Texas at Austin, Austin, Texas; and School of Molecular and Microbial Sciences (PRD), University of Queensland, St. Lucia, Australia.
    Search for more papers by this author
  • R. Dayne Mayfield

    1. From the School of Medical Science & Griffith Health Institute (JML), Griffith University, Southport, Australia; Waggoner Center for Alcohol and Addiction Research (YON, GRT, RAH, RDM), University of Texas at Austin, Austin, Texas; and School of Molecular and Microbial Sciences (PRD), University of Queensland, St. Lucia, Australia.
    Search for more papers by this author

Reprint requests: R. D. Mayfield, Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Campus Mail Code A4800, Austin, TX 78712; Tel.: 512-232-7578; Fax: 512-232-2525; E-mail: dayne.mayfield@mail.utexas.edu

Abstract

Background:  MicroRNAs (miRNAs) are small, noncoding oligonucleotides with an important role in posttranscriptional regulation of gene expression at the level of translation and mRNA degradation. Recent studies have revealed that miRNAs play important roles in a variety of biological processes, such as cell proliferation, neuronal differentiation, developmental timing, synapse function, and neurogenesis. A single miRNA can target hundreds of mRNA transcripts for either translation repression or degradation, but the function of many human miRNAs is not known.

Methods:  miRNA array analysis was performed on the prefrontal cortex of 27 individual human cases (14 alcoholics and 13 matched controls). Target genes for differentially expressed miRNAs were predicted using multiple target prediction algorithms and a consensus approach, and predicted targets were matched against differentially expressed mRNAs from the same samples. Over- and under-representation analysis was performed using hypergeometric probability and z-score tests.

Results:  Approximately 35 miRNAs were significantly up-regulated in the alcoholic group compared with controls. Target prediction showed a large degree of overlap with our published cDNA microarray data. Functional classification of the predicted target genes of the regulated miRNAs includes apoptosis, cell cycle, cell adhesion, nervous system development, and cell–cell signaling.

Conclusions:  These data suggest that the reduced expression of genes in human alcoholic cases may be because of the up-regulated miRNAs. Cellular processes fundamental to neuronal plasticity appear to represent major targets of the suggested miRNA regulation.

Ancillary