Analysis of competing endogenous RNA network identifies a poorly differentiated cancer-specific RNA signature for hepatocellular carcinoma
Analysis of competing endogenous RNA network identifies a poorly differentiated cancer-specific RNA signature for hepatocellular carcinoma
复制标题
竞争性内源性 RNA 网络分析确定了肝细胞癌的低分化癌症特异性 RNA 特征
DOI：
10.1002/jcb.29454
复制
发表时间：
2019-10-23
影响因子：
4
通讯作者：
Huang, Zilin
中科院分区：
文献类型：
--
作者：
Chen, Qi-Feng;Huang, Tao;Huang, Zilin
大量证据表明，长非编码 RNA (lncRNA) 在竞争性内源 RNA (ceRNA) 网络中发挥着至关重要的作用。低分化肝细胞癌（PDHCC）是一种恶性表型。本文旨在探讨lncRNA作为ceRNA的一种对PDHCC的作用及其潜在调控机制。此外，还评估了预后预测。共鉴定出 943 个信使 RNA (mRNA)、86 个 miRNA 和 468 个 lncRNA，它们在 137 个 PDHCC 和 235 个分化良好的 HCC 之间差异表达。此后，根据生物信息学分析，建立了与失调的lncRNA相关的ceRNA网络，包括29个lncRNA、9个miRNA和96个mRNA。 RNA 相关的总生存 (OS) 曲线使用 Kaplan-Meier 方法确定。 lncRNA ARHGEF7-AS2 与 HCC 的 OS 显着相关 (P=.041)。此外，Cox 回归分析显示，ARHGEF7-AS2 低表达的患者与显着较短的生存时间相关 (P=.038)。此外，1年、3年和5年生存率的lncRNA特征曲线下面积值分别为0.806、0.741和0.701。此外，还建立了lncRNA列线图，内部验证的C指数为0.717。体外实验证明沉默 ARHGEF7-AS2 表达可显着促进 HCC 细胞增殖和迁移。总而言之，我们的研究结果进一步阐明了 PDHCC 中与 lncRNA 相关的 ceRNA 网络，并且 ARHGEF7-AS2 可以作为预测 HCC 预后的独立生物标志物。
Plenty of evidence has suggested that long noncoding RNAs (lncRNAs) play a vital role in competing endogenous RNA (ceRNA) networks. Poorly differentiated hepatocellular carcinoma (PDHCC) is a malignant phenotype. This paper aimed to explore the effect and the underlying regulatory mechanism of lncRNAs on PDHCC as a kind of ceRNA. Additionally, prognosis prediction was assessed. A total of 943 messenger RNAs (mRNAs), 86 miRNAs, and 468 lncRNAs that were differentially expressed between 137 PDHCCs and 235 well-differentiated HCCs were identified. Thereafter, a ceRNA network related to the dysregulated lncRNAs was established according to bioinformatic analysis and included 29 lncRNAs, 9 miRNAs, and 96 mRNAs. RNA-related overall survival (OS) curves were determined using the Kaplan-Meier method. The lncRNA ARHGEF7-AS2 was markedly correlated with OS in HCC (P=.041). Moreover, Cox regression analysis revealed that patients with low ARHGEF7-AS2 expression were associated with notably shorter survival time (P=.038). In addition, the area under the curve values of the lncRNA signature for 1-, 3-, and 5-year survival were 0.806, 0.741, and 0.701, respectively. Furthermore, a lncRNA nomogram was established, and the C-index of the internal validation was 0.717. In vitro experiments were performed to demonstrate that silencing ARHGEF7-AS2 expression significantly promoted HCC cell proliferation and migration. Taken together, our findings shed more light on the ceRNA network related to lncRNAs in PDHCC, and ARHGEF7-AS2 may be used as an independent biomarker to predict the prognosis of HCC.