Long Noncoding RNA Expression Signatures of Colon Cancer Based on the ceRNA Network and Their Prognostic Value
Long Noncoding RNA Expression Signatures of Colon Cancer Based on the ceRNA Network and Their Prognostic Value
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基于 ceRNA 网络的结肠癌长非编码 RNA 表达特征及其预后价值
DOI：
10.1155/2019/7636757
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Zhu, Yun
中科院分区：
文献类型：
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作者：
Cheng, Yang;Geng, Lanlan;Zhu, Yun
长链非编码RNA（lncRNA）作为ceRNA在结肠癌中的特定功能作用及其对结肠癌预后的潜在意义尚不清楚。在本研究中，进行了全基因组分析，以研究基于“ceRNA假说”的潜在lncRNA介导的ceRNA在结肠癌中的相互作用。评估lncRNA的预后价值。方法基于miRNA、lncRNA和mRNA的表达谱，结合miRNA调控网络，采用整合计算方法构建一个与lncRNA相关的ceRNA网络。分子生物学技术，包括qPCR和基因敲低技术，用于验证结肠癌中的候选靶点。进行存活分析以鉴定具有预后价值的候选lncRNA。结果我们的网络分析发现了一些新的lncRNA作为功能性ceRNA通过与miRNA的串扰。患者组织以及基因敲低结肠癌细胞的QRT-PCR测定证实了顶级lncRNA的表达及其与ceRNA网络中靶基因的相关性。功能富集分析预测差异表达的lncRNA可能参与与肿瘤进展相关的广泛生物学功能。此外，这些lncRNA可能参与一系列细胞途径，包括细胞凋亡、PI 3 K-AKT和EGFR信号传导途径。生存分析显示，网络中几种lncRNA的表达水平与结肠癌患者的预后相关。结论本研究揭示了结肠癌中lncRNA相关的ceRNA网络失调。初步探讨了这些lncRNA在结肠癌中的功能，并评估了其潜在的预后价值。我们的研究表明，lncRNA可能在结肠癌的发生和发展中起重要的调节作用。鉴定了结肠癌中的候选预后lncRNA生物标志物。
Background The specific functional roles of long noncoding RNAs (lncRNAs) as ceRNAs in colon cancer and their potential implications for colon cancer prognosis remain unclear. In the present study, a genome-wide analysis was performed to investigate the potential lncRNA-mediated ceRNA interplay in colon cancer based on the “ceRNA hypothesis.” The prognostic value of the lncRNAs was evaluated. Methods A dysregulated lncRNA-associated ceRNA network was constructed based on the miRNA, lncRNA, and mRNA expression profiles in combination with the miRNA regulatory network by using an integrative computational method. Molecular biological techniques, including qPCR and gene knockdown techniques, were used to verify candidate targets in colon cancer. Survival analysis was performed to identify the candidate lncRNAs with prognostic value. Results Our network analysis uncovered several novel lncRNAs as functional ceRNAs through crosstalk with miRNAs. The QRT-PCR assays of patient tissues as well as gene knockdown colon cancer cells confirmed the expression of top lncRNAs and their correlation with target genes in the ceRNA network. Functional enrichment analysis predicted that differentially expressed lncRNAs might participate in broad biological functions associated with tumor progression. Moreover, these lncRNAs may be involved in a range of cellular pathways, including the apoptosis, PI3K-AKT, and EGFR signaling pathways. The survival analysis showed that the expression level of several lncRNAs in the network was correlated with the prognosis of patients with colon cancer. Conclusions This study uncovered a dysregulated lncRNA-associated ceRNA network in colon cancer. The function of the identified lncRNAs in colon cancer was preliminarily explored, and their potential prognostic value was evaluated. Our study demonstrated that lncRNAs could potentially serve as important regulators in the development and progression of colon cancer. Candidate prognostic lncRNA biomarkers in colon cancer were identified.