Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1

Cancer Res. 2008 Nov 1;68(21):8976-85. doi: 10.1158/0008-5472.CAN-08-0769.

Abstract

A role for microRNAs (miRNA) in human T-cell leukemia virus 1 (HTLV-1)-mediated cellular transformation has not been described. Here, we profiled miRNA expression in HTLV-1-transformed human T-cell lines and primary peripheral blood mononuclear cells from adult T-cell leukemia patients. Analyses of 11 different profiles revealed six miRNAs that were consistently up-regulated. Two of the up-regulated miRNAs (miR-93 and miR-130b) target the 3' untranslated region (3'UTR) of the mRNA for a tumor suppressor protein, tumor protein 53-induced nuclear protein 1 (TP53INP1). A low expression level of TP53INP1 protein was found in HTLV-1-transformed cells. Additionally, when antagomirs were used to knock down miR-93 and miR-130b in these cells, the expression of TP53INP1 was increased, suggesting that the latter is regulated inside cells by the former. A role for TP53INP1 in regulating cell growth was established by experiments that showed that enhanced TP53INP1 expression increased apoptosis. Collectively, the findings implicate a miR-93/miR-130b-TP53INP1 axis that affects the proliferation and survival of HTLV-1-infected/transformed cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Division / physiology*
  • Cell Line, Transformed
  • DNA Primers
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / physiology*
  • Human T-lymphotropic virus 1 / physiology*
  • In Situ Nick-End Labeling
  • Leukemia / genetics
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Polymerase Chain Reaction

Substances

  • 3' Untranslated Regions
  • Carrier Proteins
  • DNA Primers
  • Heat-Shock Proteins
  • MicroRNAs
  • TP53INP1 protein, human