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构建 ceRNA 网络并综合分析肝细胞癌中的 lncRNA。

Construction of a ceRNA Network and Comprehensive Analysis of lncRNA in Hepatocellular Carcinoma.

机构信息

Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230026, China.

出版信息

Genes (Basel). 2022 Apr 28;13(5):785. doi: 10.3390/genes13050785.

Abstract

To explore the RNA biomolecular marker associated with hepatocellular carcinoma (HCC) prognosis, we constructed a regulatory network of competitive endogenous RNAs (ceRNAs), which provides favorable conditions for the early diagnosis, prognostic monitoring, and personalized treatment of HCC. In this study, the differentially expressed genes (DEGs) of patients with HCC were obtained from the Gene Expression Omnibus. We identified 574 upregulated genes and 274 downregulated genes relevant to HCC occurrence (p < 0.05). Subsequently, we constructed the protein−protein interaction (PPI) network using these DEGs and identified the hub genes from the PPI. We then determined the expression and prognostic values of the hub genes from the GEPIA and Kaplan−Meier plotter databases. After the upstream microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were respectively identified by miRTarBase and miRNet, we validated the expression of the key miRNAs in the serum using qPCR experiments. Moreover, we identified a two-lncRNA (LINC01184 and ADORA2A-AS1) signature from the upstream lncRNA that effectively predicted overall survival and had promotive effects for HCC. To verify the clinical significance of the signature, we validated the expression of the lncRNA in HCC tissues. Finally, we discovered and identified four mRNAs, four miRNAs, and five lncRNAs associated with the prognosis of HCC and constructed a new ceRNA regulatory network, which will be beneficial for the accurate diagnosis and treatment of HCC.

摘要

为了探索与肝细胞癌(HCC)预后相关的 RNA 生物标志物,我们构建了竞争性内源性 RNA(ceRNA)的调控网络,为 HCC 的早期诊断、预后监测和个体化治疗提供了有利条件。在本研究中,我们从基因表达综合数据库中获得了 HCC 患者的差异表达基因(DEGs)。我们鉴定了 574 个上调基因和 274 个与 HCC 发生相关的下调基因(p < 0.05)。随后,我们使用这些 DEGs 构建了蛋白质-蛋白质相互作用(PPI)网络,并从 PPI 中确定了枢纽基因。然后,我们从 GEPIA 和 Kaplan-Meier plotter 数据库中确定了枢纽基因的表达和预后价值。在分别通过 miRTarBase 和 miRNet 确定了上游 microRNAs(miRNAs)和长链非编码 RNA(lncRNAs)后,我们使用 qPCR 实验验证了关键 miRNAs 在血清中的表达。此外,我们从上游 lncRNA 中鉴定出了一个由两个 lncRNA(LINC01184 和 ADORA2A-AS1)组成的特征,该特征可以有效地预测总体生存率,并对 HCC 具有促进作用。为了验证该特征的临床意义,我们在 HCC 组织中验证了 lncRNA 的表达。最后,我们发现并鉴定了与 HCC 预后相关的四个 mRNAs、四个 miRNAs 和五个 lncRNAs,并构建了一个新的 ceRNA 调控网络,这将有助于 HCC 的准确诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd0/9141944/d7ba66e4d6db/genes-13-00785-g001.jpg

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