Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue
Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue
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DOI：
10.1186/s12885-019-5983-8
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发表时间：
2019-08-07
期刊：
影响因子：
3.8
通讯作者：
Tang, Ying
中科院分区：
文献类型：
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作者：
Zhou, Rui-Sheng;Zhang, En-Xin;Tang, Ying
背景大量研究表明，长链非编码RNA（lncRNA）可以作为竞争性内源RNA（ceRNA）与microRNA（miRNA）位点结合，从而影响和调节mRNA和靶基因的表达。理论上这些 lncRNA 相关的 ceRNA 在癌症的发生和进展中发挥着重要作用。然而，lncRNA-miRNA-mRNA ceRNA网络在舌鳞状细胞癌（SCCT）中的作用和功能仍不清楚。方法从癌症基因组图谱数据库下载 138 例 SCCT 患者的 miRNA、mRNA 和 lncRNA 表达谱。我们使用 R 软件的 limma 包识别了 miRNA、mRNA 和 lncRNA 的差异表达。我们使用 clusterProfiler 包进行 GO 和 KEGG 通路注释。生存包用于根据 Kaplan-Meier 曲线估计生存分析。最后，使用GDCRNATools包构建lncRNA-miRNA-mRNA ceRNA网络。结果总共探索了 1943 个 SCCT 特异性 mRNA、107 个 lncRNA 和 100 个 miRNA。 10 个 mRNA（CSRP2、CKS2、ADGRG6、MB21D1、GMNN、RIPOR3、RAD51、PCLAF、ORC1、NAGS）、9 个 lncRNA（LINC02560、HOXC13 - AS、FOXD2 - AS1、AC105277.1、AC099850.3、STARD4 - AS1、SLC16A1 - AS1、MIR503HG、MIR100HG）和 8 个 miRNA（miR - 654、miR - 503、miR - 450a、miR - 379、miR - 369、miR - 190a、miR - 101 和 let-7c）被发现与总生存率显着相关（对数秩 p < 0.05）。基于lncRNA-miRNA-mRNA ceRNA网络的分析，1个差异表达（DE）lncRNA、5个DEmiRNA和3个DEmRNA被证明与SCCT的发病机制相关。结论 在本研究中，我们描述了 lncRNA-miRNA-mRNA ceRNA 网络在 SCCT 进展中的基因调控。我们提出了一种新的 lncRNA 相关 ceRNA，可以帮助 SCCT 的诊断和治疗。
Background Numerous studies have highlighted that long non-coding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competing endogenous RNAs (ceRNAs), thereby affecting and regulating the expression of mRNAs and target genes. These lncRNA-associated ceRNAs have been theorized to play a significant role in cancer initiation and progression. However, the roles and functions of the lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of the tongue (SCCT) are still unclear. Methods The miRNA, mRNA and lncRNA expression profiles from 138 patients with SCCT were downloaded from The Cancer Genome Atlas database. We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the limma package of R software. We used the clusterProfiler package for GO and KEGG pathway annotations. The survival package was used to estimate survival analysis according to the Kaplan-Meier curve. Finally, the GDCRNATools package was used to construct the lncRNA-miRNA-mRNA ceRNA network. Results In total, 1943 SCCT-specific mRNAs, 107 lncRNAs and 100 miRNAs were explored. Ten mRNAs (CSRP2, CKS2, ADGRG6, MB21D1, GMNN, RIPOR3, RAD51, PCLAF, ORC1, NAGS), 9 lncRNAs (LINC02560, HOXC13 - AS, FOXD2 - AS1, AC105277.1, AC099850.3, STARD4 - AS1, SLC16A1 - AS1, MIR503HG, MIR100HG) and 8 miRNAs (miR - 654, miR - 503, miR - 450a, miR - 379, miR - 369, miR - 190a, miR - 101, and let-7c) were found to be significantly associated with overall survival (log-rank p < 0.05). Based on the analysis of the lncRNA-miRNA-mRNA ceRNA network, one differentially expressed (DE) lncRNA, five DEmiRNAs, and three DEmRNAs were demonstrated to be related to the pathogenesis of SCCT. Conclusions In this study, we described the gene regulation by the lncRNA-miRNA-mRNA ceRNA network in the progression of SCCT. We propose a new lncRNA-associated ceRNA that could help in the diagnosis and treatment of SCCT.