The Role of Gene Expression Changes in ceRNA Network Underlying Ossification of Ligamentum Flavum Development
The Role of Gene Expression Changes in ceRNA Network Underlying Ossification of Ligamentum Flavum Development
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ceRNA网络中基因表达变化在黄韧带发育骨化中的作用
DOI：
10.1089/dna.2020.5446
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发表时间：
2020
影响因子：
3.1
通讯作者：
Liang Jie
中科院分区：
文献类型：
--
作者：
Wu Weifei;Chen Ying;Yang Zong;Zhang Fan;Ru Neng;Wu Bin;Nie Ke;Liang Jie
目的探讨非编码RNA调控的基因表达变化在黄韧带骨化中的作用。从公共基因表达综合库下载三个微阵列数据集，包括长非编码RNA（lncRNA）/mRNA表达谱（GSE 106253）、环状RNA（circRNA）表达谱（GSE 106255）和微小RNA（miRNA）表达谱（GSE 106256）。分析OLF组织中与正常组织相比差异表达（DE）的mRNA、lncRNA、miRNAs和circRNA。分别构建了具有lncRNA-miRNA-mRNA和circRNA-miRNA-mRNA相互作用的两个竞争性内源RNA（ceRNA）网络。应用随机游走再启动模型计算mRNA与已发表的OLF相关基因的相关性。对前50个mRNA进行功能富集分析和活性小分子预测。基于微阵列数据集，总共鉴定了2323个DE mRNA、1168个lncRNA、336个circRNA和29个miRNA。LncRNA相关的ceRNA网络由614个lncRNA-miRNA、494个miRNA-mRNA和2099个lncRNA-mRNA相互作用对构建; circRNA相关的ceRNA网络由153个circRNA-miRNA、190个miRNA-mRNA和210个circRNA-mRNA相互作用对构建。从文献中检索到17个OLF相关基因，包括NPPS、COL 6A 1和COL 11 A2，其中COL 6A 1是与ceRNA网络中mRNA重叠的基因。随后，捕获ceRNA网络中与COL 6A 1密切相关的前50个mRNA，这些基因与胶原分解代谢过程、细胞生长调节和神经元动作电位密切相关。DRD 1和COL 6A 1有望成为小分子药物的靶点。胶原分解代谢过程可能与OLF的发生有关。COL 6A 1和DRD 1可能是OLF的候选靶点。然而，还需要进一步验证。
We aimed at exploring the role of gene expression changes regulated by non-coding RNAs in ossification of ligamentum flavum (OLF). Three microarray datasets, including long non-coding RNA (lncRNA)/mRNA expression profile (GSE106253), circular RNA (circRNA) expression profile (GSE106255), and microRNA (miRNA) expression profile (GSE106256), were downloaded from the public Gene Expression Omnibus repository. The differentially expressed (DE) mRNAs, lncRNAs, miRNAs, and circRNAs in OLF tissues were analyzed, compared with normal tissues. Two competing endogenous RNA (ceRNA) networks with lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA interactions were constructed, separately. Random walk with the restart model was applied to calculate the correlations of mRNAs with the published OLF-related genes. The top 50 mRNAs were subjected to function enrichment analysis and active small-molecule prediction. Total 2323 DE mRNAs, 1168 lncRNAs, 336 circRNAs, and 29 miRNAs were identified based on the microarray datasets. The LncRNA-related ceRNA network was constructed with 614 lncRNA-miRNA, 494 miRNA-mRNA, and 2099 lncRNA-mRNA interaction pairs; the circRNA-related ceRNA network was constructed with 153 circRNA-miRNA, 190 miRNA-mRNA, and 210 circRNA-mRNA interaction pairs. There were 17 OLF-related genes retrieved from previous literature, such as NPPS, COL6A1, and COL11A2, among which COL6A1 was the overlapped gene with mRNAs in the ceRNA network. Subsequently, top 50 mRNAs that closely correlated with COL6A1 in the ceRNA network were captured and these genes were closely related with the collagen catabolic process, regulation of cell growth, and neuronal action potential. DRD1 and COL6A1 were predicted to be the targets by small active molecule drugs. The collagen catabolic process may be implicated in OLF development. COL6A1 and DRD1 may be the candidate targets for OLF. However, further validations were needed.