STAT1: A Novel Target of miR-150 and miR-223 Is Involved in the Proliferation of HTLV-I-Transformed and ATL Cells

Neoplasia. 2015 May;17(5):449-62. doi: 10.1016/j.neo.2015.04.005.


We have previously reported on the deregulation of cellular microRNAs involved in hematopoiesis and inflammation in human T-cell lymphotropic virus type 1 (HTLV-I)-transformed cells. In this study, we demonstrate that miR-150 and miR-223 specifically target the signal transducer and activator of transcription 1 (STAT1) 3' untranslated region, reducing STAT1 expression and dampening STAT1-dependent signaling in human T cells. The effects of miR-150 and miR-223 on endogenous STAT1 were confirmed using inducible cell lines. Our studies also showed that miR-150 expression is upregulated by interleukin-2 signaling in adult T cell leukemia/lymphoma (ATL) cells. HTLV-I-transformed and ATL-derived cells have reduced levels of miR150 and miR223 expression, which coincide with increased STAT1 expression and STAT1-dependent signaling. Knockdown of STAT1 by short hairpin RNA demonstrated that the constitutive activation of STAT1 is required for the continuous proliferation of HTLV-I-transformed cells. Our studies further demonstrate that increased expression of STAT1 in ATL cells is associated with higher levels of major histocompatibility complex class I expression. Previous studies have demonstrated that the pressure exerted by natural killer (NK) cells in vivo can edit leukemic tumor cells by forcing an increased expression of major histocompatibility complex class I to escape immune clearance. STAT1-expressing tumor cells produce more aggressive tumors because they cannot be eliminated by NK cells. Our results suggest that therapeutic approaches using combined targeting of STAT1 and MHC class I may be an effective approach to activate NK cell-mediated clearance of ATL tumor cells.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / immunology
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Viral / genetics
  • Gene Expression Regulation, Leukemic / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Human T-lymphotropic virus 1
  • Humans
  • Killer Cells, Natural / immunology
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / immunology
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • MicroRNAs / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT1 Transcription Factor / genetics*
  • Transfection


  • 3' Untranslated Regions
  • Histocompatibility Antigens Class I
  • MIRN150 microRNA, human
  • MIRN223 microRNA, human
  • MicroRNAs
  • STAT1 Transcription Factor
  • STAT1 protein, human