Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Oncol Rep. 2018 Mar;39(3):1197-1206. doi: 10.3892/or.2018.6207. Epub 2018 Jan 10.
Increasing evidence has experimentally proved the competitive endogenous RNA (ceRNA) hypothesis that long non-coding RNA (lncRNA) can affect the expression of RNA targets by competitively combining microRNA (miRNA) via miRNA response elements. However, an extensive ceRNA network of thyroid carcinoma in a large cohort has not been evaluated. We analyzed the RNAseq and miRNAseq data of 348 cases of primary papillary thyroid cancer (PTC) patients with clinical information downloaded from The Cancer Genome Atlas (TCGA) project to search for potential biomarkers or therapeutic targets. A computational approach was applied to build an lncRNA-miRNA-mRNA regulatory network of PTC. In total, 780 lncRNAs were detected as collectively dysregulated lncRNAs in all 3 PTC variants compared with normal tissues (fold change >2 and false discovery rate <0.05). The interactions among 45 lncRNAs, 13 miRNAs and 86 mRNAs constituted a ceRNA network of PTC. Nine out of the 45 aberrantly expressed lncRNAs were related to the clinical features of PTC patients. However, the expression levels of 3 lncRNAs (LINC00284, RBMS3-AS1 and ZFX-AS1) were identified to be tightly correlated with the patients overall survival (log-rank, P<0.05). The present study identified a list of specific lncRNAs associated with PTC progression and prognosis. This complex ceRNA interaction network in PTC may provide guidance for better understanding the molecular mechanisms underlying PTC.
越来越多的证据从实验上证实了竞争性内源性 RNA（ceRNA）假说，即长非编码 RNA（lncRNA）可以通过 miRNA 反应元件与 miRNA 竞争结合来影响 RNA 靶标的表达。然而，尚未在大型队列中评估甲状腺癌的广泛 ceRNA 网络。我们分析了 348 例原发性甲状腺乳头状癌（PTC）患者的 RNAseq 和 miRNAseq 数据，这些患者的临床信息从癌症基因组图谱（TCGA）项目中下载，以寻找潜在的生物标志物或治疗靶点。应用计算方法构建了 PTC 的 lncRNA-miRNA-mRNA 调控网络。总的来说，与正常组织相比，在所有 3 种 PTC 变体中检测到 780 个 lncRNA 作为整体失调的 lncRNA（倍数变化>2，假发现率<0.05）。在 45 个 lncRNA、13 个 miRNA 和 86 个 mRNA 之间的相互作用构成了 PTC 的 ceRNA 网络。在 45 个异常表达的 lncRNA 中有 9 个与 PTC 患者的临床特征有关。然而，3 个 lncRNA（LINC00284、RBMS3-AS1 和 ZFX-AS1）的表达水平被确定与患者的总生存率密切相关（对数秩检验，P<0.05）。本研究确定了与 PTC 进展和预后相关的一组特定 lncRNA。PTC 中这种复杂的 ceRNA 相互作用网络可能为更好地理解 PTC 的分子机制提供指导。
