Circulating miRNAs as diagnostic biomarkers for adolescent idiopathic scoliosis.
Circulating miRNAs as diagnostic biomarkers for adolescent idiopathic scoliosis.
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DOI：
10.1038/s41598-018-21146-x
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发表时间：
2018-02-08
影响因子：
4.6
通讯作者：
Bas T
中科院分区：
文献类型：
--
作者：
García-Giménez JL;Rubio-Belmar PA;Peiró-Chova L;Hervás D;González-Rodríguez D;Ibañez-Cabellos JS;Bas-Hermida P;Mena-Mollá S;García-López EM;Pallardó FV;Bas T
青少年特发性脊柱侧凸（AIS）的病因与许多因素有关，如不对称生长、神经肌肉状况、骨强度和遗传背景。最近，表观遗传因素已被提出作为AIS的病理生理学的贡献者，但有关的分子机制和途径的信息很少。关于表观遗传因子，微小RNA（miRNAs）是通过调节重要的细胞途径而有助于基因表达调节的分子。我们在本文中使用下一代测序来发现在AIS患者的血液样本中检测到的一系列循环miRNA，这产生了独特的miRNA生物标志物特征，其以高灵敏度和特异性诊断AIS。我们认为这些miRNAs通过调节成骨细胞和破骨细胞的分化参与信号通路的表观遗传控制，从而调节AIS患者的遗传背景。我们的研究产生了两个相关结果：1）参与AIS成骨细胞/破骨细胞分化机制的失调miRNA的证据; 2）该miRNA标记可潜在地用作分子AIS诊断的临床工具。使用miRNAs作为AIS诊断的生物标志物是特别相关的，因为miRNAs可以用于早期诊断和评估应用疗法的积极作用，从而减少对高风险手术干预的需求。
The aetiology of adolescent idiopathic scoliosis (AIS) has been linked to many factors, such as asymmetric growth, neuromuscular condition, bone strength and genetic background. Recently, epigenetic factors have been proposed as contributors of AIS physiopathology, but information about the molecular mechanisms and pathways involved is scarce. Regarding epigenetic factors, microRNAs (miRNAs) are molecules that contribute to gene expression modulation by regulating important cellular pathways. We herein used Next-Generation Sequencing to discover a series of circulating miRNAs detected in the blood samples of AIS patients, which yielded a unique miRNA biomarker signature that diagnoses AIS with high sensitivity and specificity. We propose that these miRNAs participate in the epigenetic control of signalling pathways by regulating osteoblast and osteoclast differentiation, thus modulating the genetic background of AIS patients. Our study yielded two relevant results: 1) evidence for the deregulated miRNAs that participate in osteoblast/osteoclast differentiation mechanisms in AIS; 2) this miRNA-signature can be potentially used as a clinical tool for molecular AIS diagnosis. Using miRNAs as biomarkers for AIS diagnostics is especially relevant since miRNAs can serve for early diagnoses and for evaluating the positive effects of applied therapies to therefore reduce the need of high-risk surgical interventions.
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