Abstract
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. 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. 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. MiR-17 inhibits melanoma growth by stimulating CD8+ T cells mediated host immune response, which is due to its regulation of STAT3.
Highlights
Melanoma is the most aggressive skin cancer, and is characterized by its rapid growth and early metastasis
Our studies show that STAT3 mediates the function of miR-17 in regulating T-cell activities, providing novel insight into the mechanisms that may underlie immune evasion in melanoma cells
In tumor-infiltrating T cells, we found higher percentages of CD8+ cells in the miR-17 transgenic mice compared with the wild type (Figure 4d)
Summary
Melanoma is the most aggressive skin cancer, and is characterized by its rapid growth and early metastasis. It accounts for over 75% of deaths related to skin cancer. Melanoma has one of the fastest growing incidences in North America, and it has been steadily increasing for the past 30 years. It is estimated that 2% of Caucasians will develop melanoma in their lifetime [1]. In 2014, approximately 76,100 new cases will be diagnosed and about 9,710 individuals will die from melanoma in the United States [1]. 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
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