构建并综合分析 ceRNA 网络，揭示肺腺癌潜在的预后生物标志物。
Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma.
机构信息
Department of Respiratory and Critical Care Medicine, The Second Hospital of Anhui Medical University, 678 Furong Road, Economic And Technological Development Zone, Hefei, 230601, Anhui Province, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, 230022, Anhui Province, China.
出版信息
BMC Cancer. 2021 Jul 23;21(1):849. doi: 10.1186/s12885-021-08462-8.
BACKGROUND
More and more studies have proven that circular RNAs (circRNAs) play vital roles in cancer development via sponging miRNAs. However, the expression pattern of competing endogenous RNA (ceRNA) in lung adenocarcinoma (LUAD) remains largely unclear. The current study explored functional roles and the regulatory mechanisms of circRNA as ceRNAs in LUAD and their potential impact on LUAD patient prognosis.
METHODS
In this study, we systematically screened differential expression circRNAs (DEcircRNAs), miRNAs (DEmiRNAs) and mRNAs (DEGs) associated with LUAD. Then, DEcircRNAs, DEmiRNAs and DEGs were selected to construct a circRNA-miRNA-mRNA prognosis-related regulatory network based on interaction information from the ENCORI database. Subsequently, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the genes in the network to predict the potential underlying mechanisms and functions of circRNAs in LUAD. In addition, Kaplan-Meier survival analysis was performed to evaluate clinical outcomes of LUAD patients, and drug sensitivity analysis was used to screen potential biomarkers for drug treatment of patients with LUAD.
RESULTS
As a result, 10 circRNAs were aberrantly expressed in LUAD tissues. The ceRNA network was built, which included 3 DEcircRNAs, 6 DEmiRNAs and 157 DEGs. The DEGs in the ceRNA network of hsa_circ_0049271 enriched in biological processes of cell proliferation and the Jak-STAT signaling pathway. We also detected 7 mRNAs in the ceRNA network of hsa_circ_0049271 that were significantly associated with the overall survival of LUAD patients (P < 0.05). Importantly, four genes (PDGFB, CCND2, CTF1, IL7R) identified were strongly associated with STAT3 activation and drugs sensitivity in GDSC.
CONCLUSIONS
In summary, a ceRNA network of hsa_circ_0049271 was successfully constructed, which including one circRNA, two miRNAs, and seven mRNAs. Seven mRNAs (PDGFB, TNFRSF19, CCND2, CTF1, IL11RA, IL7R and MAOA) were remarkably associated with the prognosis of LUAD patients. Among seven mRNA species, four genes (PDGFB, CCND2, CTF1, and IL7R) could be considered as drug targets in LUAD. Our research will provide new insights into the prognosis-related ceRNA network in LUAD.
背景
越来越多的研究证明，环状 RNA（circRNAs）通过海绵吸附 miRNA 在癌症发展中发挥重要作用。然而，肺腺癌（LUAD）中竞争内源性 RNA（ceRNA）的表达模式在很大程度上仍不清楚。本研究旨在探讨 circRNA 作为 ceRNA 在 LUAD 中的功能作用和调控机制及其对 LUAD 患者预后的潜在影响。
方法
在本研究中，我们系统地筛选了与 LUAD 相关的差异表达 circRNAs（DEcircRNAs）、miRNAs（DEmiRNAs）和 mRNAs（DEGs）。然后，根据 ENCORI 数据库中的相互作用信息，选择 DEcircRNAs、DEmiRNAs 和 DEGs 构建 circRNA-miRNA-mRNA 预后相关调控网络。随后，对网络中的基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，以预测 circRNAs 在 LUAD 中的潜在作用机制和功能。此外，进行 Kaplan-Meier 生存分析以评估 LUAD 患者的临床结局，并进行药物敏感性分析以筛选 LUAD 患者药物治疗的潜在生物标志物。
结果
结果显示，在 LUAD 组织中存在 10 个异常表达的 circRNAs。构建了 ceRNA 网络，其中包括 3 个 DEcircRNAs、6 个 DEmiRNAs 和 157 个 DEGs。ceRNA 网络中的 DEGs 在细胞增殖的生物学过程和 Jak-STAT 信号通路中富集。我们还检测到 ceRNA 网络中的 7 个 mRNAs 与 LUAD 患者的总生存期显著相关（P<0.05）。重要的是，在 GDSC 中，鉴定出的 4 个基因（PDGFB、CCND2、CTF1、IL7R）与 STAT3 激活和药物敏感性密切相关。
结论
总之，成功构建了 hsa_circ_0049271 的 ceRNA 网络，其中包括一个 circRNA、两个 miRNA 和七个 mRNAs。七个 mRNAs（PDGFB、TNFRSF19、CCND2、CTF1、IL11RA、IL7R 和 MAOA）与 LUAD 患者的预后显著相关。在七个 mRNA 中，有 4 个基因（PDGFB、CCND2、CTF1 和 IL7R）可被视为 LUAD 的药物靶点。我们的研究将为 LUAD 中预后相关 ceRNA 网络提供新的见解。
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