Key result
MIR409-3p expression was decreased in PBMCs of active ITP patients due to down-regulated DGCR8, leading to up-regulation of IFNG, and recovered after effective therapy.
Observational
In primary immune thrombocytopenia, decreased DGCR8 down-regulates MIR409-3p, which up-regulates IFNG, suggesting a novel epigenetic mechanism in ITP pathogenesis.
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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).
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miR-409-3p downregulation in active ITP may mark immune dysregulation; leaves open biomarker or therapeutic potential pending larger prospective studies.
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Li et al. (2013) conducted an observational in Primary immune thrombocytopenia (ITP). MIR409-3p expression was evaluated on MIR409-3p expression levels and target genes. MIR409-3p expression was decreased in PBMCs of active ITP patients due to down-regulated DGCR8, leading to up-regulation of IFNG, and recovered after effective therapy.
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