MiR-34a is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation through the SIRT1/NFκB pathway

FEBS Lett. 2012 Nov 30;586(23):4203-7. doi: 10.1016/j.febslet.2012.10.023. Epub 2012 Oct 24.

Abstract

MicroRNAs (miRNAs) regulate gene expression and may contribute to HIV-1 infection. In this study, our goal was to investigate the mechanisms by which miR-34a influenced Tat-induced HIV-1 transactivation through the SIRT1/NFκB pathway. We showed that Tat induced up-regulation of miR-34a expression in TZM-bl cells. MiR-34a significantly inhibited SIRT1 expression. Overexpression of miR-34a increased Tat-induced LTR transactivation. Forced expression of miR-34a decreased SIRT1 protein expression and consequently diminished Tat-induced acetylation of p65, while treatment with a miR-34a inhibitor had the opposite effect. These results suggest that regulating SIRT1 by down-regulation of miR-34a levels may be a therapeutic strategy against HIV-1 replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • HIV Long Terminal Repeat / genetics*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • MicroRNAs
  • NF-kappa B
  • tat Gene Products, Human Immunodeficiency Virus
  • SIRT1 protein, human
  • Sirtuin 1