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miR-150-5p 通过靶向 Bach2 调节重型再生障碍性贫血中的 T 细胞活化。

MiR-150-5p regulate T cell activation in severe aplastic anemia by targeting Bach2.

机构信息

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Henan Province, Zhengzhou, 450052, China.

出版信息

Cell Tissue Res. 2021 May;384(2):423-434. doi: 10.1007/s00441-020-03373-9. Epub 2021 Jan 15.

Abstract

MiR-150-5p is an immune-related miRNA and elevated in the plasma of patients with aplastic anemia (AA), but its role in T cell activation in patients with severe aplastic anemia (SAA) is unclear. This study aims to explore the role of miR-150-5p in T cell activation of SAA. RT-PCR and Western blot were used to detect the expression of mRNA and protein. The cell proportion was detected by flow cytometry. The lentiviruses expressing miR-150-5p inhibitor and Bach2 shRNA were respectively infected to produce stable miR-150-5p or Bach2 knockout cells. Brdu incorporation method was used to detect T cell proliferation. SAA mouse model was induced with cyclophosphamide and busulfan, and intravenous injection of LV inhibitor NC and LV-miR-150-5p inhibitor. The miR-150-5p expression is up-regulated in SAA, which is negatively correlated with Bach2. Inhibition of miR-150-5p reduces the activation of T cells. MiR-150-5p directly targeted 3'UTR of Bach2. Moreover, the expression of miR-150-5p and the activation of T cells were decreased in SAA mouse model. MiR-150-5p promotes T cell activation in SAA by targeting Bach2. Targeting miR-150-5p may be a new molecular therapy for SAA patients.

摘要

miR-150-5p 是一种免疫相关的 microRNA,在再生障碍性贫血(AA)患者的血浆中升高,但它在严重再生障碍性贫血(SAA)患者 T 细胞激活中的作用尚不清楚。本研究旨在探讨 miR-150-5p 在 SAA T 细胞激活中的作用。采用 RT-PCR 和 Western blot 检测 mRNA 和蛋白的表达。采用流式细胞术检测细胞比例。分别用表达 miR-150-5p 抑制剂和 Bach2 shRNA 的慢病毒感染产生稳定的 miR-150-5p 或 Bach2 敲除细胞。 Brdu 掺入法检测 T 细胞增殖。用环磷酰胺和白消安诱导 SAA 小鼠模型,静脉注射 LV 抑制剂 NC 和 LV-miR-150-5p 抑制剂。SAA 中 miR-150-5p 表达上调,与 Bach2 呈负相关。抑制 miR-150-5p 可降低 T 细胞的激活。miR-150-5p 可直接靶向 Bach2 的 3'UTR。此外,SAA 小鼠模型中 miR-150-5p 的表达和 T 细胞的激活均降低。miR-150-5p 通过靶向 Bach2 促进 SAA 中 T 细胞的激活。针对 miR-150-5p 可能是 SAA 患者的一种新的分子治疗方法。

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