Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing.
Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing.
复制标题
集成的 microRNA-mRNA 分析揭示了使用高通量测序的 OPLL 特异性 microRNA 调控网络
DOI：
10.1038/srep21580
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发表时间：
2016-02-12
影响因子：
4.6
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Xu C;Chen Y;Zhang H;Chen Y;Shen X;Shi C;Liu Y;Yuan W
后纵韧带骨化症是一种遗传性疾病，是脊柱韧带的病理性异位骨化。虽然研究已经确定了几个与OPLL相关的基因，但潜在的调控网络还远未清楚。通过小分子RNA测序，我们比较了OPLL患者和正常患者（PLL）的原代后纵韧带细胞的microRNA表达，鉴定出218个失调的miRNAs（FDR < 0.01）。此外，评估多种细胞类型的miRNA谱数据，我们发现这些失调的miRNA大多是OPLL特异性的。为了破译这些OPLL特异性miRNA的调控网络，我们整合了mRNA表达谱数据和miRNA测序数据。通过计算方法，我们发现了与骨骼系统发育、胶原纤维组织和细胞外基质组织相关的高度相关的miRNA/mRNA对，从而显示了这些OPLL特异性miRNA在纵韧带异位骨化中的关键作用。这些结果为我们建立的miRNA调控网络在OPLL的发生和发展中发挥重要作用提供了强有力的证据。迄今为止，这是第一个系统的分析的微小组在OPLL，因此可能会提供宝贵的资源，在寻找新的治疗和诊断目标的OPLL。
Ossification of the posterior longitudinal ligament (OPLL) is a genetic disorder which involves pathological heterotopic ossification of the spinal ligaments. Although studies have identified several genes that correlated with OPLL, the underlying regulation network is far from clear. Through small RNA sequencing, we compared the microRNA expressions of primary posterior longitudinal ligament cells form OPLL patients with normal patients (PLL) and identified 218 dysregulated miRNAs (FDR < 0.01). Furthermore, assessing the miRNA profiling data of multiple cell types, we found these dysregulated miRNAs were mostly OPLL specific. In order to decipher the regulation network of these OPLL specific miRNAs, we integrated mRNA expression profiling data with miRNA sequencing data. Through computational approaches, we showed the pivotal roles of these OPLL specific miRNAs in heterotopic ossification of longitudinal ligament by discovering highly correlated miRNA/mRNA pairs that associated with skeletal system development, collagen fibril organization, and extracellular matrix organization. The results of which provide strong evidence that the miRNA regulatory networks we established may indeed play vital roles in OPLL onset and progression. To date, this is the first systematic analysis of the micronome in OPLL, and thus may provide valuable resources in finding novel treatment and diagnostic targets of OPLL.