4.7 Article

MicroRNA-491 regulates the proliferation and apoptosis of CD8+ T cells

Journal

SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/srep30923

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Funding

  1. National Natural Science Foundation of China [81202310]
  2. Chongqing Youth Science and Technology Talent Training Project [cstc2014kjrc-qnrc10008]

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T lymphocyte-mediated immune responses are critical for antitumour immunity; however, T cell function is impaired in the tumour environment. MicroRNAs are involved in regulation of the immune system. While little is known about the function of intrinsic microRNAs in CD8(+) T cells in the tumour microenvironment. Here, we found that miR-491 was upregulated in CD8(+) T cells from mice with colorectal cancer. Retroviral overexpression of miR-491 in CD8+ and CD4(+) T cells inhibited cell proliferation and promoted cell apoptosis and decreased the production of interferon-gamma in CD8(+) T cells. We found that miR-491 directly targeted cyclin-dependent kinase 4, the transcription factor T cell factor 1 and the anti-apoptotic protein B-cell lymphoma 2-like 1 in CD8(+) T cells. Furthermore, tumour-derived TGF-beta induced miR-491 expression in CD8(+) T cells. Taken together, our results suggest that miR-491 can act as a negative regulator of T lymphocytes, especially CD8(+) T cells, in the tumour environment; thus, this study provides a novel insight on dysfunctional CD8(+) T cells during tumourigenesis and cancer progression. In conclusion, miR-491 may be a new target for antitumour immunotherapy.

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