Identification of circular RNA-microRNA-messenger RNA regulatory network in hepatocellular carcinoma by integrated analysis
Identification of circular RNA-microRNA-messenger RNA regulatory network in hepatocellular carcinoma by integrated analysis
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DOI：
10.1111/jgh.14762
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发表时间：
2019-07-18
影响因子：
4.1
通讯作者：
Chen, Dongfeng
中科院分区：
文献类型：
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作者：
Sun, Xiangjun;Ge, Xinfeng;Chen, Dongfeng
背景与目的肝细胞癌（HCC）是最常见的肝脏恶性肿瘤。本研究的目的是更好地了解肝癌的发病机制，可能有助于提高肝癌的诊断水平。方法收集美国癌症基因组图谱数据库（The Cancer Genome Atlas）中肝癌组织的mRNA和miRNA表达谱，以及Gene Expression Omnibus数据库中肝癌组织的circRNA表达谱，进行综合分析。鉴定差异表达的mRNA（DEmRNAs）、差异表达的miRNA（DEmiRNAs）和差异表达的circRNAs（DEcircRNAs），构建竞争性内源RNA（ceRNA）（DEcircRNA-DEmiRNA-DEmRNAs）调控网络。对ceRNA调控网络中DEcircRNA和DEmRNAs的宿主基因进行功能注释。对所选DEmRNA、DEmiRNA和DEcircRNA的表达进行定量实时聚合酶链反应验证。结果共获得DEmRNA 2982条，DEmiRNA 144条，DEcircRNA 264条。ceRNA网络包含61个circRNA-miRNA对和1149个miRNA-mRNA对，包括48个circRNA、30个miRNA和1149个mRNAs。在ceRNA调控网络中对DEmRNAs的功能注释显示，这些DEmRNAs在色氨酸代谢、脂肪酸代谢和癌症通路中显著富集。除ARNT 2和hsa-miR-214- 3 p外，其他基因的表达量与我们的综合分析结果基本一致。结论hsa_circRNA_104268/hsa-miR-214- 3 p/E2 F2、hsa_circRNA_104168/hsa-miR-139- 5 p/HRAS和hsa_circRNA_104769/hsa-miR-93- 5 p/JUN相互作用对可能在HCC中起重要作用。本研究有望从circRNA-miRNA-mRNA网络的角度为肝癌的发病机制和治疗提供新的思路。
Background and Aim Hepatocellular carcinoma (HCC) is the most common types of hepatic malignancies. This study aimed to better understand the pathogenesis of HCC and may help facilitate the improvement of the diagnostic of HCC. Methods The mRNA and miRNA expression profiles of HCC, which was retrieved from The Cancer Genome Atlas database, and the circRNA expression profiles of HCC, which was retrieved from Gene Expression Omnibus database, were included in this study to perform an integrated analysis. The differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and competing endogenous RNA (ceRNA) (DEcircRNA-DEmiRNA-DEmRNA) regulatory network was conducted. Functional annotation of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. Quantitative real-time polymerase chain reaction validation of the expression of the selected DEmRNAs, DEmiRNAs, and DEcircRNAs was performed. Results A total of 2982 DEmRNAs, 144 DEmiRNAs, and 264 DEcircRNAs were obtained. The ceRNA network contained 61 circRNA-miRNA pairs and 1149 miRNA-mRNA pairs, including 48 circRNAs, 30 miRNAs, and 1149 mRNAs. Functional annotation of DEmRNAs in ceRNA regulatory network revealed that these DEmRNAs were significantly enriched in tryptophan metabolism, fatty acid metabolism, and pathways in cancer. Except for ARNT2 and hsa-miR-214-3p, expression of the others in the quantitative real-time polymerase chain reaction results was consistent with that in our integrated analysis, generally. Conclusion We speculate that hsa_circRNA_104268/hsa-miR-214-3p/E2F2, hsa_circRNA_104168/hsa-miR-139-5p/HRAS, and hsa_circRNA_104769/hsa-miR-93-5p/JUN interaction pairs may play a vital role in HCC. This study expected to provide a novel insight into the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.