Zhang Junjie, Lou Weiyang
Department of Hepatobiliary Surgery, The First People's Hospital of Fuyang Hangzhou, Hangzhou, China.
Department of Breast Surgery, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, China.
Front Oncol. 2020 Mar 17;10:340. doi: 10.3389/fonc.2020.00340. eCollection 2020.
Growing evidence has illustrated critical roles of competing endogenous RNA (ceRNA) regulatory network in human cancers including hepatocellular carcinoma. In this study, we aimed to find promising diagnostic and prognostic biomarkers for patients with hepatocellular carcinoma. Three novel unfavorable prognosis-associated genes (CELSR3, GPSM2, and CHEK1) was first identified. We also demonstrated that these genes were significantly upregulated in hepatocellular carcinoma cell lines and tissues. Next, 154 potential miRNAs of CELSR3, GPSM2, and CHEK1 were predicted. CHEK1-hsa-mir-195-5p/hsa-mir-497-5p and GPSM2-hsa-mir-122-5p axes were defined as two key pathways in carcinogenesis of hepatocellular carcinoma by combination of analysis and experimental validation. Subsequently, lncRNAs binding to hsa-mir-195-5p, hsa-mir-497-5p, and hsa-mir-122-5p were predicted via starBase and miRNet databases. After performing expression analysis and survival analysis for these predicted lncRNAs, we showed that nine lncRNAs (SNHG1, SNHG12, LINC00511, HCG18, FGD5-AS1, CERS6-AS1, NUTM2A-AS1, SNHG16, and ASB16-AS1) were markedly increased in hepatocellular carcinoma and their upregulation indicated poor prognosis. Moreover, a similar mRNA-miRNA-lncRNA analysis for six "known" genes (CLEC3B, DNASE1L3, PTTG1, KIF2C, XPO5, and UBE2S) was performed. Subsequently, a comprehensive mRNA-miRNA-lncRNA triple ceRNA network linked to prognosis of patients with hepatocellular carcinoma was established. Moreover, all RNAs in this network exhibited significantly diagnostic values for patients with hepatocellular carcinoma. In summary, the current study constructed a mRNA-miRNA-lncRNA ceRNA network associated with diagnosis and prognosis of hepatocellular carcinoma.
越来越多的证据表明，竞争性内源性RNA（ceRNA）调控网络在包括肝细胞癌在内的人类癌症中发挥着关键作用。在本研究中，我们旨在寻找肝细胞癌患者有前景的诊断和预后生物标志物。首先鉴定出三个新的与不良预后相关的基因（CELSR3、GPSM2和CHEK1）。我们还证明这些基因在肝癌细胞系和组织中显著上调。接下来，预测了CELSR3、GPSM2和CHEK1的154个潜在miRNA。通过分析和实验验证相结合，CHEK1-hsa-mir-195-5p/hsa-mir-497-5p和GPSM2-hsa-mir-122-5p轴被定义为肝细胞癌发生的两个关键途径。随后，通过starBase和miRNet数据库预测与hsa-mir-195-5p、hsa-mir-497-5p和hsa-mir-122-5p结合的lncRNA。对这些预测的lncRNA进行表达分析和生存分析后，我们发现九个lncRNA（SNHG1、SNHG12、LINC00511、HCG18、FGD5-AS1、CERS6-AS1、NUTM2A-AS1、SNHG16和ASB16-AS1）在肝细胞癌中显著增加，它们的上调表明预后不良。此外，对六个“已知”基因（CLEC3B、DNASE1L3、PTTG1、KIF2C、XPO5和UBE2S）进行了类似的mRNA-miRNA-lncRNA分析。随后，建立了一个与肝细胞癌患者预后相关的综合mRNA-miRNA-lncRNA三重ceRNA网络。此外，该网络中的所有RNA对肝细胞癌患者均具有显著的诊断价值。总之，本研究构建了一个与肝细胞癌诊断和预后相关的mRNA-miRNA-lncRNA ceRNA网络。
