Construction and investigation of lncRNA-associated ceRNA regulatory network in papillary thyroid cancer.

Construction and investigation of lncRNA-associated ceRNA regulatory network in papillary thyroid cancer.
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甲状腺乳头状癌lncRNA相关ceRNA调控网络的构建与研究。

DOI:
10.3892/or.2018.6207
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发表时间:
2018-03
期刊:
影响因子:
4.2
通讯作者:
Shao Q
Shao Q
中科院分区:
医学3区
文献类型:
--
作者:
Zhao Y;Wang H;Wu C;Yan M;Wu H;Wang J;Yang X;Shao Q

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越来越多的证据通过实验证明了竞争性内源 RNA (ceRNA) 假说,即长非编码 RNA (lncRNA) 可以通过 miRNA 响应元件竞争性结合 microRNA (miRNA) 来影响 RNA 靶标的表达。然而,尚未对大型队列中甲状腺癌的广泛 ceRNA 网络进行评估。我们分析了 348 例原发性甲状腺乳头状癌 (PTC) 患者的 RNAseq 和 miRNAseq 数据以及从癌症基因组图谱 (TCGA) 项目下载的临床信息,以寻找潜在的生物标志物或治疗靶点。应用计算方法构建 PTC 的 lncRNA-miRNA-mRNA 调控网络。与正常组织相比,在所有 3 种 PTC 变体中,总共有 780 个 lncRNA 被检测为集体失调的 lncRNA(倍数变化 >2 且错误发现率 <0.05)。 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。 45 个异常表达的 lncRNA 中有 9 个与 PTC 患者的临床特征相关。然而,3种lncRNA(LINC00284、RBMS3-AS1和ZFX-AS1)的表达水平被确定与患者的总生存期密切相关(对数秩,P<0.05)。本研究确定了一系列与 PTC 进展和预后相关的特定 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。
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.
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