Large-scale analyses identify a cluster of novel long noncoding RNAs as potential competitive endogenous RNAs in progression of hepatocellular carcinoma
Large-scale analyses identify a cluster of novel long noncoding RNAs as potential competitive endogenous RNAs in progression of hepatocellular carcinoma
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大规模分析确定了一组新型长非编码 RNA 作为肝细胞癌进展中潜在的竞争性内源性 RNA。
DOI：
10.18632/aging.102468
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发表时间：
2019-11-30
期刊：
影响因子：
5.2
通讯作者：
Xia, Jian-Chuan
中科院分区：
文献类型：
--
作者：
Song, Mengjia;Zhong, Ailin;Xia, Jian-Chuan
非编码RNA的异常表达在肝细胞癌进展领域引起了越来越多的关注。然而，在这些过程中由非编码RNA介导的潜在分子机制尚不清楚。在这里，我们从基因表达综合数据库中获得了长链非编码RNA、microRNA和mRNA的表达谱，并鉴定了肝癌发生特异性差异表达的转录本。接下来，我们确定了差异表达转录本涉及的重要基因本体和途径术语。利用功能分析和靶点预测，我们构建了一个肝细胞癌相关的去调控竞争性内源性RNA网络，以揭示肿瘤进展的潜在机制。通过分析癌症基因组图谱数据集，六个关键的长非编码RNA显示出与总生存率的显著相关性，以及与竞争性内源性RNA网络中的一些microRNA和mRNA的强相关性。我们进一步验证了上述结果，并确定了它们在临床样本中的诊断和预后价值。重要的是，通过大规模分析，我们确定了一组长非编码RNA，GBAP 1，MCM 3AP-AS 1，SLC 16 A1-AS 1，C3 P1，DIO 3 OS和HNF 4A-AS 1作为肝细胞癌诊断和预后的候选生物标志物，这将提高我们对竞争性内源性RNA介导的肝细胞癌发展调控机制的理解，并将在未来提供新的治疗靶点。
The abnormal expression of noncoding RNAs has attracted increasing interest in the field of hepatocellular carcinoma progression. However, the underlying molecular mechanisms mediated by noncoding RNAs in these processes are unclear. Here, we obtained the expression profiles of long noncoding RNAs, microRNAs, and mRNAs from the Gene Expression Omnibus database and identified hepatocarcinogenesis-specific differentially expressed transcripts. Next, we identified significant Gene Ontology and pathway terms that the differentially expressed transcripts involved in. Using functional analysis and target prediction, we constructed a hepatocellular carcinoma-associated deregulated competitive endogenous RNA network to reveal the potential mechanisms underlying tumor progression. By analyzing The Cancer Genome Atlas dataset, six key long noncoding RNAs showed significant association with overall survival as well as strong correlation with some microRNAs and mRNAs in the competitive endogenous RNA network. We further validated the above results and determined their diagnostic and prognostic value in clinical samples. Importantly, by large-scale analyses, we identified a cluster of long noncoding RNAs, GBAP1, MCM3AP-AS1, SLC16A1-AS1, C3P1, DIO3OS, and HNF4A-AS1 as candidate biomarkers for the diagnosis and prognosis of hepatocellular carcinoma, which will improve our understanding of competitive endogenous RNA-mediated regulatory mechanisms underlying hepatocellular carcinoma development and will provide novel therapeutic targets in the future.