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miRNA-7 过表达通过靶向 PIK3R1 正向调控 CD8 SP 细胞的发育。

MicroRNA-7 overexpression positively regulates the CD8 SP cell development via targeting PIK3R1.

机构信息

Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Guizhou, 563000, China; Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Guizhou, 563000, China.

Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Guizhou, 563000, China; Department of Medical Physics, Zunyi Medical University, Zunyi, Guizhou, 563003, China.

出版信息

Exp Cell Res. 2021 Oct 15;407(2):112824. doi: 10.1016/j.yexcr.2021.112824. Epub 2021 Sep 10.

Abstract

microRNA-7 (miR-7), a distinct miRNA family member, has been reported to be involved in the biological functions of immune cells. However, the potential role of miR-7 in the CD8 T cell development remains to be elucidated. In this study, we estimated the potential effects of miR-7 overexpression in the thymic CD8 SP cell development using miR-7 overexpression mice. Our results showed that compared with those in control wild type (WT) mice, the volume, weight and total cell numbers of thymus in miR-7 overexpression (OE) mice increased significantly. The absolute cell number of CD8 SP cells in miR-7 OE mice increased and its ability of activation and proliferation enhanced. Futhermore, we clarified that miR-7 overexpression had an intrinsic promote role in CD8 SP cell development by adoptive cell transfer assay. Mechanistically, the expression level of PIK3R1, a target of miR-7, decreased significantly in CD8 SP cells of miR-7 OE mice. Moreover, the expression level of phosphorylated (p)-AKT and p-ERK changed inversely and indicating that miR-7 overexpression impaired the balance of AKE and ERK pathways. In summary, our work reveals an essential role of miR-7 in promoting CD8 SP cell development through the regulation of PIK3R1 and balance of AKT and ERK pathways.

摘要

miR-7(miR-7),一个独特的 miRNA 家族成员,已被报道参与免疫细胞的生物学功能。然而,miR-7 在 CD8 T 细胞发育中的潜在作用仍有待阐明。在这项研究中,我们使用 miR-7 过表达小鼠来评估 miR-7 过表达对胸腺 CD8 SP 细胞发育的潜在影响。我们的结果表明,与对照野生型(WT)小鼠相比,miR-7 过表达(OE)小鼠的胸腺体积、重量和总细胞数显著增加。miR-7 OE 小鼠的 CD8 SP 细胞绝对数量增加,其激活和增殖能力增强。此外,我们通过细胞转移实验阐明了 miR-7 过表达对 CD8 SP 细胞发育具有内在的促进作用。从机制上讲,miR-7 的靶标 PIK3R1 的表达水平在 miR-7 OE 小鼠的 CD8 SP 细胞中显著降低。此外,磷酸化(p)-AKT 和 p-ERK 的表达水平呈相反变化,表明 miR-7 过表达破坏了 AKT 和 ERK 途径的平衡。总之,我们的工作揭示了 miR-7 通过调节 PIK3R1 和 AKT 和 ERK 途径的平衡在促进 CD8 SP 细胞发育中的重要作用。

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