title: MicroRNA-17 inhibits tumor growth by stimulating T-cell mediated host immune response.
abstract: BACKGROUND
  Melanoma is one of the fastest-rising types of cancer in North American. Accumulating evidence suggests that anti-tumor immune tolerance plays a critical role in tumor development.
  
  
  METHODS
  B16 melanoma cells were injected into wild type and miR-17 overexpressing transgenic mice. Tumor growth was monitored and tumor bearing mice were sacrificed by the end of the forth week. Peripheral blood and spleen cells were subject to flow cytometry analysis and tumor samples were subject to immunohistochemistry staining. Meanwhile, Jurkat cells transfected with mock-control or miR-17 overexpressing plasmid were co-cultured with B16 cells. The influence of miR-17 on cell cycle, proliferation and survival was evaluated.
  
  
  RESULTS
  The melanoma tumors formed in mice overexpressing miR-17 were less than that in wild type mice. In addition, the miR-17 tumors were less invasive and less angiogenic. The percentage of CD8+ T cells was suppressed in miR-17 transgenic mice before melanoma cell injection. Its level was significantly increased upon tumor grafting. More tumor infiltrating CD8+ cytotoxic T lymphocyte could be found in transgenic mice with tumor formation. Luciferase assay and protein analysis indicated that STAT3 was the target of miR-17. Decreased levels of STAT3 were associated with miR-17 over-expression. Down-regulation of STAT3 in Jurkat cells promoted cell proliferation and mitosis.
  
  
  CONCLUSIONS
  MiR-17 inhibits melanoma growth by stimulating CD8+ T cells mediated host immune response, which is due to its regulation of STAT3.
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto.
authors.forename: Haoran
authors.initials: H
authors.lastname: Li
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto.
authors.forename: Shaan
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto.
authors.forename: William W
authors.initials: WW
authors.lastname: Du
authors.affiliation: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto.
authors.forename: Burton B
authors.initials: BB
authors.lastname: Yang
keywords: Stat3; T-cell; immune response; miR-17; microRNA