title: MicroRNA-491 regulates the proliferation and apoptosis of CD8(+) T cells.
abstract: 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.
authors.affiliation: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qian-Fei
authors.initials: QF
authors.lastname: Zuo
authors.affiliation: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.affiliation: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wang
authors.affiliation: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Quan-Ming
authors.initials: QM
authors.lastname: Zou
authors.affiliation: National Engineering Research Center of Immunological Products &Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D051017:Apoptosis Regulatory Proteins; C551675:MIRN491 microRNA, mouse; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma