Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study.
Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study.
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人类椎间盘退变中异常表达的长非编码 RNA：一项微阵列相关研究。
DOI：
10.1186/s13075-014-0465-5
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发表时间：
2014-10-04
影响因子：
4.9
通讯作者：
Luo ZJ
中科院分区：
文献类型：
--
作者：
Wan ZY;Song F;Sun Z;Chen YF;Zhang WL;Samartzis D;Ma CJ;Che L;Liu X;Ali MA;Wang HQ;Luo ZJ
除了众所周知的短非编码RNA，如microRNAs(MiRNAs)，越来越多的证据表明，长非编码RNAs(LncRNAs)在生物过程的广泛方面发挥关键调节作用。研究表明，lncRNAs的异常表达与多种人类疾病有关。然而，关于lncRNAs在椎间盘退变(IDD)中的作用，我们知之甚少。在本研究中，我们的目的是确定lncRNAs在IDD中是否存在差异表达。采用人髓核(NP)LncRNA-mRNA微阵列分析方法。生物信息学预测也被用来描述差异表达的lncRNA的功能作用。选择几个lncRNAs和mRNAs进行定量实时聚合酶链式反应(qRT-PCR)验证。微阵列数据图谱显示，116个lncRNAs(67个上调，49个下调)和260个mRNAs高度差异表达，绝对折叠变化大于10。此外，在折叠变化大于2的5个变性样本中，至少有4个样本在同一方向上有1,052个lncRNA和1,314个mRNAs的差异表达。京都基因和基因组百科全书(KEGG)对差异表达的mRNAs进行的途径分析表明，有许多途径，如细胞外基质(ECM)-受体相互作用。构建了编码-非编码基因共表达网络，分析了10个最显著变化的lncRNAs。共表达的mRNAs的注释术语与几种已知的退行性改变有关，如软骨细胞分化。此外，还鉴定了属于特定亚组的lncRNAs。对邻近编码基因的功能注释表明，这些lncRNAs主要与细胞迁移和磷酸化有关。有趣的是，我们发现促进Fas介导的细胞凋亡的Fas相关蛋白因子-1(FAF1)及其附近的增强子样LncRNA RP11-296A18.3在退变的椎间盘中高表达。随后的qRT-PCR结果证实了这些变化。这是第一个证明异常表达的lncRNAs在IDD的发生发展中起作用的研究。我们的研究发现，上调的RP11-296A18.3很可能诱导了FAF1的过度表达，最终促进了椎间盘细胞的异常凋亡。这些发现进一步扩大了对IDD病因的理解。本文的在线版本(doi：10.1186/s13075-0140465-5)包含补充材料，授权用户可以使用。
In addition to the well-known short noncoding RNAs such as microRNAs (miRNAs), increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, little is known regarding the role of lncRNAs with regards to intervertebral disc degeneration (IDD). In the present study we aimed to determine whether lncRNAs are differentially expressed in IDD. An lncRNA-mRNA microarray analysis of human nucleus pulposus (NP) was employed. Bioinformatics prediction was also applied to delineate the functional roles of the differentially expressed lncRNAs. Several lncRNAs and mRNAs were chosen for quantitative real-time PCR (qRT-PCR) validation. Microarray data profiling indicated that 116 lncRNAs (67 up and 49 down) and 260 mRNAs were highly differentially expressed with an absolute fold change greater than ten. Moreover, 1,052 lncRNAs and 1,314 mRNAs were differentially expressed in the same direction in at least four of the five degenerative samples with fold change greater than two. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated a number of pathways, such as extracellular matrix (ECM)-receptor interaction. A coding-noncoding gene co-expression (CNC) network was constructed for the ten most significantly changed lncRNAs. Annotation terms of the coexpressed mRNAs were related to several known degenerative alterations, such as chondrocyte differentiation. Moreover, lncRNAs belonging to a particular subgroup were identified. Functional annotation for the corresponding nearby coding genes showed that these lncRNAs were mainly associated with cell migration and phosphorylation. Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes. This is the first study to demonstrate that aberrantly expressed lncRNAs play a role in the development of IDD. Our study noted that up-regulated RP11-296A18.3 highly likely induced the over-expression of FAF1, which eventually promoted the aberrant apoptosis of disc cells. Such findings further broaden the understanding of the etiology of IDD. The online version of this article (doi:10.1186/s13075-014-0465-5) contains supplementary material, which is available to authorized users.
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