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原发性免疫性血小板减少症中 MIR409-3p 的表达降低。

Reduced expression of MIR409-3p in primary immune thrombocytopenia.

机构信息

State Key Laboratory of Experimental Haematology, Institute of Haematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

出版信息

Br J Haematol. 2013 Apr;161(1):128-35. doi: 10.1111/bjh.12213. Epub 2013 Jan 30.

Abstract

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with many immune dysfunctions. MicroRNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally regulate gene expression by messenger RNA degradation or translational repression. Accumulating evidence has demonstrated that miRNAs play a vital role in the regulation of immunological functions and prevention of autoimmunity. However, whether miRNAs are involved in the pathogenesis of ITP is still unknown. To illustrate the role of miRNAs in ITP, the expression profile of miRNAs from peripheral blood mononuclear cells (PBMCs) in ITP patients was investigated by miRNA microarray, and further validated by TaqMan real-time polymerase chain reaction. MIR409-3p expression was decreased in PBMCs of active ITP patients, but this recovered after effective therapy. IFNG was identified and validated as one of the targeted genes of MIR409-3p by bioinformatic prediction and reporter gene analysis. In addition, we found DGCR8 transcript was down-regulated in ITP patients and positively correlated with MIR409-3p. Thus, in ITP patients, decreased DGCR8 leads to down-regulation of MIR409-3p, which in turn results in up-regulation of IFNG (IFN-γ).

摘要

原发性免疫性血小板减少症(ITP)是一种获得性自身免疫性疾病,存在多种免疫功能紊乱。microRNAs(miRNAs)是一类非编码 RNA,通过信使 RNA 降解或翻译抑制来进行转录后基因表达调控。越来越多的证据表明,miRNAs 在调节免疫功能和预防自身免疫中起着至关重要的作用。然而,miRNAs 是否参与 ITP 的发病机制尚不清楚。为了阐明 miRNAs 在 ITP 中的作用,通过 miRNA 微阵列研究了 ITP 患者外周血单个核细胞(PBMC)中的 miRNA 表达谱,并通过 TaqMan 实时聚合酶链反应进一步验证。MIR409-3p 在活动性 ITP 患者的 PBMC 中表达降低,但在有效治疗后恢复。通过生物信息学预测和报告基因分析鉴定并验证 IFNG 是 MIR409-3p 的靶向基因之一。此外,我们发现 ITP 患者的 DGCR8 转录本下调,与 MIR409-3p 呈正相关。因此,在 ITP 患者中,DGCR8 的减少导致 MIR409-3p 的下调,进而导致 IFNG(IFN-γ)的上调。

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