Wu Ping, Xiao Yunyue, Guo Tao, Wang Yitao, Liao Shanshan, Chen Lang, Liu Zhisu
Department of Hepatobiliary and Pancreas, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, P.R. China.
Institute of Digestive, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
J Cancer. 2019 Jun 2;10(11):2552-2559. doi: 10.7150/jca.28167. eCollection 2019.
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.
越来越多的证据表明，微小RNA（miRNA）与肝细胞癌（HCC）有关。为了鉴定参与肝癌发生的新型可行的miRNA/mRNA对，本研究对人类非肿瘤肝脏和HCC样本中的miRNA组进行了深入分析。首先，从15个肝脏样本的深度测序中获得差异表达的miRNA，并在来自癌症基因组图谱（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靶标，并筛选出具有负相关性的差异miRNA/mRNA对。最后，使用功能富集分析来预测miRNA/mRNA对在HCC中的功能。在我们的研究中，发现了81个miRNA/mRNA对和7个新型miRNA。我们构建了一个包含9个miRNA/mRNA对的枢纽相互作用模型，以进一步研究HCC的分子机制。生存分析确定了9个对HCC患者预后有显著影响的基因（hsa-miR-137、hsa-miR-490、BIRC5、TOP2A、CDC25C、IGF2BP1、IQGAP3、NCAPG和VIPR1）。总之，我们研究中鉴定出的miRNA/mRNA对可能在HCC的进展、诊断和预后方面具有一些有待进一步研究的潜在价值。
