Identifying miRNA-mRNA Pairs and Novel miRNAs from Hepatocelluar Carcinoma miRNomes and TCGA Database
Identifying miRNA-mRNA Pairs and Novel miRNAs from Hepatocelluar Carcinoma miRNomes and TCGA Database
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DOI：
10.7150/jca.28167
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Liu, Zhisu
中科院分区：
文献类型：
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作者：
Wu, Ping;Xiao, Yunyue;Liu, Zhisu
越来越多的证据表明，microRNAs （miRNAs）参与肝细胞癌（HCC）。为了寻找新的可能参与肝癌发生的miRNA/mRNA对，本研究对人类非肿瘤肝脏和HCC样本中的miRNomes进行了深入分析。首先，从15个肝脏样本的深度测序中获得差异表达的mirna，并在癌症基因组图谱（TCGA）数据库的独立数据中进行验证。然后，从TCGA中选择差异表达的mRNA靶点，筛选出负相关的差异miRNA/mRNA对。最后，通过功能富集分析预测miRNA/mRNA对在HCC中的功能。在我们的研究中，发现了81对miRNA/mRNA和7对新的miRNA。我们构建了包含9对miRNA/mRNA的枢纽相互作用模型，进一步探讨HCC的分子机制。生存分析发现9个基因（hsa-miR-137、hsa-miR-490、BIRC5、TOP2A、CDC25C、IGF2BP1、IQGAP3、NCAPG和VIPR1）对HCC患者预后有显著影响。综上所述，本研究发现的miRNA/mRNA对在HCC的进展、诊断和预后方面可能具有一定的潜在价值，值得进一步研究。
Increasing evidence shows microRNAs (miRNAs) are engaged in hepatocelluar carcinoma (HCC). To identify novel feasible miRNA/mRNA pairs involved in hepatocarcinogenesis, an in-depth analysis of miRNomes in human non-tumor liver and HCC samples was carried out in this study. Firstly, differentially expressed miRNAs were obtained from deep sequencing of 15 liver samples, and verified in an independent data from The Cancer Genome Atlas (TCGA) database. Then, differentially expressed mRNA targets were selected from TCGA, and the differential miRNA/mRNA pairs with negative correlations were screened out. Finally, functional enrichment analysis was used to predict the functions of miRNA/mRNA pairs in HCC. In our study, 81 miRNA/mRNA pairs and 7 novel miRNAs were found. We constructed a hub interaction model with 9 miRNA/mRNA pairs to further investigate molecular mechanism of HCC. Survival analysis identified nine genes (hsa-miR-137, hsa-miR-490, BIRC5, TOP2A, CDC25C, IGF2BP1, IQGAP3, NCAPG and VIPR1) with significant influence on prognosis of HCC patients. In conclusion, the miRNA/mRNA pairs identified in our study may have some potential values to be further studied in progression, diagnosis and prognosis of HCC.