Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin, China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820985787. doi: 10.1177/1533033820985787.
This study aims to construct a systematic mRNA-miRNA-lncRNA network to identify novel lncRNAs and miRNAs biomarkers for laryngeal squamous cell carcinoma (LSCC).
The mRNA, miRNA and lncRNA expression profiles of LSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were screened between LSCC tissues and controls. Functional analysis of DEmRNAs, DEmRNAs targeted by DEmiRNAs and DEmRNAs targeted by DElncRNAs were respectively performed. The miRWalk, starbase and DIANA-LncBase were respectively used to predict DEmiRNAs-DEmRNAs, DElncRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. ceRNA network was built by DEmiRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. LncRNA subcellular localization was predicted using lncLocator. Using published The Cancer Genome Atlas (TCGA) and external datasets (GSE127165 and GSE133632), we also validated the expression of key DElncRNAs and DEmiRNAs in ceRNA network. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively.
There were 5 mRNA datasets, 3 miRNA datasets and 2 lncRNA datasets in this study. Totally, 2957 DEmRNAs, 61 DElncRNAs and 23 DEmiRNAs were identified. Functional analysis of DEmRNAs shows that they were significantly enriched in cancer-related pathways, such as DNA replication and extracellular matrix organization. There were 11 DEmiRNAs, 17 DElncRNAs and 967 DEmRNAs in the ceRNA network. Notably, up-regulated lncRNA DGCR5-down-regulated has-miR-338-3p/has-miR-139-5p pairs in this network were experimentally validated. Moreover, down-regulated AL121839.2, down-regulated LINC02147, up-regulated AC079328.2, up-regulated AC004943.2 and up-regulated HMGA2-AS1 were located in the cytoplasm. AL121839.2 and LINC02147 interacted with has-miR-1246. AC004943.2, AC079328.2 and HMGA2-AS1 targeted has-miR-3185, has-miR-3137 and has-miR-582-5p, respectively. Based on the TCGA and external datasets (GSE127165 and GSE133632), DGCR5 and AC004943.2 were significantly up-regulated while AL121839.2 and LINC02147, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p were significantly down-regulated, which were consistent with our integration analysis. DGCR5, AL121839.2, LINC02147, AC004943.2, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p could predict the occurrence of LSCC. Survival analysis suggested that only, AL121839.2 has potential prognostic value for LSCC.
This study provided novel insights into the ceRNA network and uncovered novel lncRNAs and miRNAs with diagnostic value in LSCC.
本研究旨在构建一个系统的 mRNA-miRNA-lncRNA 网络，以鉴定喉鳞状细胞癌（LSCC）的新型 lncRNA 和 miRNA 生物标志物。
从基因表达综合数据库（GEO）数据库中获取 LSCC 的 mRNA、miRNA 和 lncRNA 表达谱。筛选 LSCC 组织与对照之间差异表达的 mRNAs、miRNAs 和 lncRNAs（DEmRNAs、DEmiRNAs 和 DElncRNAs）。分别对 DEmRNAs、DEmiRNAs 靶向的 DEmRNAs 和 DEmRNAs 靶向的 DElncRNAs 进行功能分析。分别使用 miRWalk、starbase 和 DIANA-LncBase 预测 DEmiRNAs-DEmRNAs、DElncRNAs-DEmRNAs 和 DElncRNAs-DEmiRNAs 对。通过 DEmiRNAs-DEmRNAs 和 DElncRNAs-DEmiRNAs 对构建 ceRNA 网络。使用 lncLocator 预测 lncRNA 的亚细胞定位。利用已发表的癌症基因组图谱（TCGA）和外部数据集（GSE127165 和 GSE133632），我们还验证了 ceRNA 网络中关键 DElncRNAs 和 DEmiRNAs 的表达。分别通过 ROC 曲线分析和生存分析评估候选基因的诊断和预后价值。
本研究共纳入 5 个 mRNA 数据集、3 个 miRNA 数据集和 2 个 lncRNA 数据集。共鉴定出 2957 个 DEmRNAs、61 个 DElncRNAs 和 23 个 DEmiRNAs。DEmRNAs 的功能分析表明，它们显著富集于癌症相关通路，如 DNA 复制和细胞外基质组织。ceRNA 网络中存在 11 个 DEmiRNAs、17 个 DElncRNAs 和 967 个 DEmRNAs。值得注意的是，该网络中上调的 lncRNA DGCR5-下调的 has-miR-338-3p/has-miR-139-5p 对经实验验证。此外，下调的 AL121839.2、下调的 LINC02147、上调的 AC079328.2、上调的 AC004943.2 和上调的 HMGA2-AS1 位于细胞质中。AL121839.2 和 LINC02147 与 has-miR-1246 相互作用。AC004943.2、AC079328.2 和 HMGA2-AS1 分别靶向 has-miR-3185、has-miR-3137 和 has-miR-582-5p。基于 TCGA 和外部数据集（GSE127165 和 GSE133632），DGCR5 和 AC004943.2 显著上调，而 AL121839.2 和 LINC02147、has-miR-338-3p、has-miR-139-5p 和 has-miR-582-5p 显著下调，与我们的整合分析结果一致。DGCR5、AL121839.2、LINC02147、AC004943.2、has-miR-338-3p、has-miR-139-5p 和 has-miR-582-5p 可预测 LSCC 的发生。生存分析表明，只有 AL121839.2 对 LSCC 具有潜在的预后价值。
本研究为 ceRNA 网络提供了新的见解，并揭示了在 LSCC 中具有诊断价值的新型 lncRNA 和 miRNA。
