Potential role of microRNA‑223‑3p in the tumorigenesis of hepatocellular carcinoma: A comprehensive study based on data mining and bioinformatics.

Potential role of microRNA‑223‑3p in the tumorigenesis of hepatocellular carcinoma: A comprehensive study based on data mining and bioinformatics.
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microRNA-223-3p在肝细胞癌肿瘤发生中的潜在作用:基于数据挖掘和生物信息学的综合研究

DOI:
10.3892/mmr.2017.8167
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发表时间:
2018-03
影响因子:
3.4
通讯作者:
Feng ZB
Feng ZB
中科院分区:
医学4区
文献类型:
--
作者:
Zhang R;Zhang LJ;Yang ML;Huang LS;Chen G;Feng ZB

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本研究旨在探讨microRNA-233-3p (miR)-223-3p在肝细胞癌(HCC)发生中的潜在作用,并探讨其诊断准确性和潜在的分子机制。miR-223-3p在HCC中的表达数据来自Gene expression Omnibus (GEO)。前体miR-223的数据来自癌症基因组图谱(TCGA)。通过受试者工作曲线(ROC)确定miR-223-3p的诊断作用,并根据文献中合格的报道计算miR-223-3p在HCC中的诊断价值。此外,将GEO、TCGA和合格实验的相关数据汇总进行综合meta分析。在线预测数据库、自然语言处理和TCGA差异表达基因之间的交叉基因被认为是miR-223-3p在HCC中的潜在靶点。利用Database for Annotation, Visualization and Integrated Discovery对潜在靶点进行基因本体富集分析和京都基因与基因组百科全书路径分析。利用相互作用基因检索工具绘制蛋白质-蛋白质相互作用图谱。GEO提供的15组合格的微阵列数据中,有7组显示HCC组织中miR-223-3p水平明显低于非癌组织(P<0.05)。此外,5个GEO数据集显示miR-223-3p的诊断价值,曲线下面积(AUC)为bb0 0.80 (P<0.05)。计算TCGA前体miR-223的诊断准确率(AUC=0.78, P<0.05)。同样,与TCGA健康对照组相比,HCC组织中前体miR-223的下调水平更高(P<0.001)。在荟萃分析中,总ROC也计算为0.89 (95% CI, 0.85-0.91)。共提取了72个潜在靶点,主要涉及“癌症中的microRNAs”、“ATP结合”和“前列腺癌”等术语。五个潜在的靶基因被认为是HCC中miR-223-3p的枢纽基因,包括checkpoint kinase 1、DNA甲基转移酶1、杆状病毒IAP repeat containing 5、激酶家族成员23和I型胶原α1。基于TCGA,枢纽基因在HCC中表达显著上调(P<0.05)。总之,这些结果表明miR-223-3p可能在HCC癌变中起关键作用,具有较高的诊断准确性,并且可能由几个枢纽基因介导。
The aims of the present study were to examine the potential role of microRNA-233-3p (miR)-223-3p in the tumorigenesis of hepatocellular carcinoma (HCC), and to investigate its diagnostic accuracy and potential molecular mechanisms. The expression data of miR-223-3p in HCC were obtained from the Gene Expression Omnibus (GEO). Data for the precursor miR-223 were obtained from The Cancer Genome Atlas (TCGA). The diagnostic role of miR-223-3p was identified by the receiver operating curve (ROC), and the diagnostic value of miR-223-3p in HCC was calculated from qualified reports in the literature. In addition, associated data from the GEO, TCGA and qualified experiments were pooled for comprehensive meta-analysis. Genes, which intersected between online prediction databases, natural language processing and differentially expressed genes from TCGA were regarded as potential targets of miR-223-3p in HCC. The Gene Ontology enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathways of potential targets were performed using the Database for Annotation, Visualization and Integrated Discovery. The protein-protein interactions were mapped using the Search Tool for the Retrieval of Interacting Genes. Among 15 qualified microarray data sets from GEO, seven showed that a significantly lower level of miR-223-3p was present in the HCC tissues, compared with that in non-cancerous tissues (P<0.05). In addition, five GEO data sets revealed diagnostic values of miR-223-3p, with an area under the curve (AUC) of >0.80 (P<0.05). The diagnostic accuracy of the precursor miR-223 in TCGA was also calculated (AUC=0.78, P<0.05). Similarly, the precursor miR-223 showed a higher level of downregulation in HCC tissues, compared with that in healthy controls in TCGA (P<0.001). A summary ROC was also calculated as 0.89 (95% CI, 0.85–0.91) in the meta-analysis. A total of 72 potential targets were extracted, mainly involved in the terms ‘microRNAs in cancer’, ‘ATP binding’ and ‘prostate cancer’. Five potential target genes were considered the hub genes of miR-223-3p in HCC, including checkpoint kinase 1, DNA methyltransferase 1, baculoviral IAP repeat containing 5, kinesin family member 23, and collagen, type I, α1. Based on TCGA, the hub genes were significantly upregulated in HCC (P<0.05). Collectively, these results showed that miR-223-3p may be crucial in HCC carcinogenesis showing high diagnostic accuracy, and may be mediated by several hub genes.
DOI: 10.2147/ott.s108828
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影响因子: 4
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Huang WT;Wang HL;Yang H;Ren FH;Luo YH;Huang CQ;Liang YY;Liang HW;Chen G;Dang YW
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发表时间: 2017-02-28
期刊: Oncotarget
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发表时间: 2005-09-01
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