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Integrated Analysis of an lncRNA-Associated ceRNA Network Reveals Potential Biomarkers for Hepatocellular Carcinoma
Journal of Computational Biology ( IF 1.4 ) Pub Date : 2021-03-04 , DOI: 10.1089/cmb.2019.0250
Jie Yang 1 , Qing-Chun Xu 1 , Zhen-Yu Wang 1 , Xun Lu 1 , Liu-Kui Pan 1 , Jun Wu 1 , Chen Wang 1
Affiliation  

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. In this study, we aimed to explore the potential biomarkers and key regulatory pathways related to HCC using integrated bioinformatic analysis and validation. The microarray data of GSE12717 and GSE54238 were downloaded from the Gene Expression Omnibus database. A competing endogenous RNA (ceRNA) network was constructed based on potential long-noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA interactions. A total of 191 mRNAs, 8 miRNAs, and 5 lncRNAs were selected to construct the ceRNA network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict their biological functions. The PI3K-Akt signaling pathway was significantly enriched. Kaplan–Meier survival analysis based on the Gene Expression Profiling Interactive Analysis (GEPIA) database was conducted for the weighted mRNAs and lncRNAs. The results showed that SRC, GMPS, CDK2, FEN1, EZH2, ZWINT, MTHFD1L, GINS2, and MAPKAPK5-AS1 were significantly upregulated in tumor tissues. The relative expression levels of these genes were significantly upregulated in HCC patients based on the StarBase database. For further validation, the expression levels of these genes were detected by real-time quantitative reverse transcription-polymerase chain reaction in 20 HCC tumor tissues and paired paracancerous tissues. Receiver operating characteristic analysis revealed that CDK2, MTHFD1L, SRC, ZWINT, and MAPKAPK5-AS1 had significant diagnostic value in HCC, but further studies are needed to explore their mechanisms in HCC.

中文翻译:

lncRNA 相关 ceRNA 网络的综合分析揭示了肝细胞癌的潜在生物标志物

肝细胞癌(HCC)是世界范围内常见的恶性肿瘤。在本研究中,我们旨在使用综合生物信息学分析和验证来探索与 HCC 相关的潜在生物标志物和关键调控途径。GSE12717和GSE54238的微阵列数据从基因表达综合数据库下载。基于潜在的长链非编码 RNA (lncRNA)-microRNA (miRNA)-mRNA 相互作用构建了竞争性内源 RNA (ceRNA) 网络。共选择191个mRNAs、8个miRNAs和5个lncRNAs构建ceRNA网络。基因本体论和京都基因和基因组百科全书(KEGG)通路分析被用来预测它们的生物学功能。PI3K-Akt 信号通路显着丰富。对加权的 mRNA 和 lncRNA 进行了基于基因表达谱交互分析 (GEPIA) 数据库的 Kaplan-Meier 生存分析。结果表明,SRC、GMPS、CDK2、FEN1、EZH2、ZWINT、MTHFD1L、GINS2和MAPKAPK5-AS1在肿瘤组织中显着上调。根据 StarBase 数据库,这些基因的相对表达水平在 HCC 患者中显着上调。为了进一步验证,通过实时定量逆转录聚合酶链反应在 20 个 HCC 肿瘤组织和配对的癌旁组织中检测这些基因的表达水平。接受者操作特征分析显示CDK2、MTHFD1L、SRC、ZWINT和MAPKAPK5-AS1在HCC中具有显着的诊断价值,但需要进一步研究以探索它们在HCC中的机制。
更新日期:2021-03-05
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