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

• Published in: Scientific reports 2016-08, Vol.6 (1), p.30923-30923, Article 30923
• Main Authors: Yu, Ting, Zuo, Qian-Fei, Gong, Li, Wang, Li-Na, Zou, Quan-Ming, Xiao, Bin
• Format: Article
• Language: English
• Subjects: 13/109; 13/2; 13/21; 13/31; 38/109; 38/47; 38/77; 42/44; 631/250/580; 631/67/580; Animals; Apoptosis; Apoptosis Regulatory Proteins - metabolism; B-cell lymphoma; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell proliferation; Cells, Cultured; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Cyclin-dependent kinase; Cyclin-dependent kinase 4; Cyclin-dependent kinases; Female; Humanities and Social Sciences; Immune response; Immune system; Immunotherapy; Interferon-gamma - metabolism; Kinases; Lymphocyte Activation; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - genetics; miRNA; multidisciplinary; Protein B; Science; Transforming Growth Factor beta - metabolism; Tumor Microenvironment; Tumorigenesis; Tumors; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep30923

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-γ 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-β 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.