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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-? 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-? 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.

SUBMITTER: Yu T

PROVIDER: S-EPMC4971478 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Yu Ting T Zuo Qian-Fei QF Gong Li L Wang Li-Na LN Zou Quan-Ming QM Xiao Bin B

Scientific reports 20160803

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 prolifera ...[more]

PMID: 27484289

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Project description:BackgroundThe number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets.MethodsStreptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA and mRNA sequencing. Through bioinformatics analysis, we constructed an miRNA-mRNA diabetic testicular damage regulatory network and screened for key miRNAs. We also used Leydig cells to generate a diabetic cell model and detected the downstream target genes of miRNAs, secretion of testosterone, and proliferation and apoptotic levels to elucidate the role and mechanism of the selected miRNAs in diabetic testicular damage.ResultsUsing second-generation sequencing, we identified 19 differentially expressed miRNAs and 555 mRNAs in the testes of diabetic rats. Based on computational prediction of targets and negative regulation relationships, we constructed a miRNA-mRNA regulatory network, including 12 miRNAs and 215 mRNAs. KEGG enrichment analysis revealed that genes were more concentrated on the survival signalling pathway. Based on this, we screened 2 key miRNAs, miR-504 and miR-935. In vitro, glucose could induce an increase in miR-504 and miR-935, whereas a decrease in MEK5 and MEF2C in a dose-dependent manner. Overexpression of miR-504 and miR-935 led to the decreased expression of MEK5 and MEF2C, decreased proliferation rate of Leydig cells, increased apoptotic rate, and decreased secretion of testosterone. Whereas, knockdown of miR-504 and miR-935 displayed opposite tendencies.ConclusionsmiRNAs play important roles in diabetic testicular damage. miR-504 and miR-935 might regulate testicular damage through the classic survival pathway of MEK5-ERK5-MEF2C. Targeted inhibition of miR-504 and miR-935 could reverse the high-glucose-induced testicular complications, thus posing as a potential therapeutic approach in diabetic testicular injury.

Dataset Information

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

Publications

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

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