Computational identifying and characterizing circular RNAs and their associated genes in hepatocellular carcinoma.
Computational identifying and characterizing circular RNAs and their associated genes in hepatocellular carcinoma.
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肝细胞癌中环状 RNA 及其相关基因的计算识别和表征
DOI：
10.1371/journal.pone.0174436
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Li M
中科院分区：
文献类型：
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作者：
Li Y;Dong Y;Huang Z;Kuang Q;Wu Y;Li Y;Li M
肝细胞癌（HCC）目前仍是导致死亡的主要因素，缺乏可靠的生物标志物。因此，深入了解HCC的发病机制具有重要意义。环状RNA （circRNA）的出现为研究人类疾病的发病机制提供了新的途径。在这里，我们使用预测工具来识别基于RNA-seq数据的环状rna。然后，为了研究circRNA的生物学功能，通过GREAT将候选circRNA与蛋白质编码基因（PCGs）关联。我们发现在正常和肿瘤样本之间有显著的候选环状rna表达改变。此外，还发现与这些候选环状rna相关的PCGs在正常和肿瘤样本之间具有区别性表达模式。富集分析表明，这些PCGs主要富集于肝/心血管相关疾病，如动脉粥样硬化、心肌缺血和冠心病，并参与多种代谢过程。进一步的网络分析表明，这些PCGs在调节和PPI网络中发挥重要作用。最后，我们建立了一个分类模型，分别使用候选环状rna及其相关基因来区分正常和肿瘤样本。两者都获得了满意的结果（circRNA和PCG的AUC为~ 0.99）。我们的研究结果提示circRNA可能是HCC的一个关键因素，为探索HCC的发病机制提供了有用的资源。
Hepatocellular carcinoma (HCC) is currently still a major factor leading to death, lacking of reliable biomarkers. Therefore, deep understanding the pathogenesis for HCC is of great importance. The emergence of circular RNA (circRNA) provides a new way to study the pathogenesis of human disease. Here, we employed the prediction tool to identify circRNAs based on RNA-seq data. Then, to investigate the biological function of the circRNA, the candidate circRNAs were associated with the protein-coding genes (PCGs) by GREAT. We found significant candidate circRNAs expression alterations between normal and tumor samples. Additionally, the PCGs associated with these candidate circRNAs were also found have discriminative expression patterns between normal and tumor samples. The enrichment analysis illustrated that these PCGs were predominantly enriched for liver/cardiovascular-related diseases such as atherosclerosis, myocardial ischemia and coronary heart disease, and participated in various metabolic processes. Together, a further network analysis indicated that these PCGs play important roles in the regulatory and the PPI network. Finally, we built a classification model to distinguish normal and tumor samples by using candidate circRNAs and their associated genes, respectively. Both of them obtained satisfactory results (~ 0.99 of AUC for circRNA and PCG). Our findings suggested that the circRNA could be a critical factor in HCC, providing a useful resource to explore the pathogenesis of HCC.