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Expression profiling and bioinformatic analyses suggest new target genes and pathways for human hair follicle related microRNAs

机译:表达谱分析和生物信息学分析表明人毛囊相关microRNA的新靶标基因和途径

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Background Human hair follicle (HF) cycling is characterised by the tight orchestration and regulation of signalling cascades. Research shows that micro(mi)RNAs are potent regulators of these pathways. However, knowledge of the expression of miRNAs and their target genes and pathways in the human HF is limited. The objective of this study was to improve understanding of the role of miRNAs and their regulatory interactions in the human HF. Methods Expression levels of ten candidate miRNAs with reported functions in hair biology were assessed in HFs from 25 healthy male donors. MiRNA expression levels were correlated with mRNA-expression levels from the same samples. Identified target genes were tested for enrichment in biological pathways and accumulation in protein-protein interaction (PPI) networks. Results Expression in the human HF was confirmed for seven of the ten candidate miRNAs, and numerous target genes for miR-24, miR-31, and miR-106a were identified. While the latter include several genes with known functions in hair biology (e.g., ITGB1, SOX9 ), the majority have not been previously implicated (e.g., PHF1 ). Target genes were enriched in pathways of interest to hair biology, such as integrin and GnRH signalling, and the respective gene products showed accumulation in PPIs. Conclusions Further investigation of miRNA expression in the human HF, and the identification of novel miRNA target genes and pathways via the systematic integration of miRNA and mRNA expression data, may facilitate the delineation of tissue-specific regulatory interactions, and improve our understanding of both normal hair growth and the pathobiology of hair loss disorders.
机译:背景技术人毛囊(HF)循环的特征是信号级联的紧密编排和调节。研究表明,micro(mi)RNA是这些途径的有效调节剂。但是,对人类HF中miRNA及其靶基因和途径表达的了解是有限的。这项研究的目的是增进对miRNA在人类HF中的作用及其调节相互作用的了解。方法在来自25位健康男性供体的HFs中评估了十种在头发生物学中具有报道功能的候选miRNA的表达水平。 MiRNA表达水平与相同样品的mRNA表达水平相关。测试了鉴定出的靶基因的生物途径富集和蛋白质-蛋白质相互作用(PPI)网络中的积累。结果确认了十种候选miRNA中的七种在人HF中的表达,并鉴定了miR-24,miR-31和miR-106a的许多靶基因。虽然后者包括在毛发生物学中具有已知功能的几个基因(例如ITGB1,SOX9),但大多数基因以前并未涉及(例如PHF1)。靶基因丰富了毛发生物学感兴趣的途径,例如整联蛋白和GnRH信号传导,并且各个基因产物在PPI中积累。结论进一步研究人类HF中miRNA的表达,并通过系统整合miRNA和mRNA表达数据来鉴定新的miRNA靶基因和途径,可能有助于描绘组织特异性调节相互作用,并增进我们对两种正常分子的了解。头发生长和脱发疾病的病理生物学。

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