School of Life Science and Technology, Henan Institute of Science and Technology, Xinxiang, P.R. China.
Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, P.R. China.
Mol Genet Genomic Med. 2019 Nov;7(11):e971. doi: 10.1002/mgg3.971. Epub 2019 Sep 9.
Aflatoxin B1 (AFB1) exposure is a crucial factor to initiate hepatocellular carcinoma (HCC). However, comprehensive microRNA (miRNA)-message RNA (mRNA) regulatory network regarding AFB1-associated HCC is still lacking. This work was aimed to identify miRNA-mRNA network in primary human hepatocytes after AFB1 exposure.
A miRNA expression dataset GSE71540 obtained from the gene expression omnibus (GEO) was used to identify differentially expressed miRNAs (DEMs) after AFB1 exposure using GEO2R. Target genes of these DEMs were identified using TargetScan V_7.2, miRDB, PITA, miRanda, and miRTarBase. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed at Database for Annotation, Visualization and Integrated Discovery (DAVID). miRNA-mRNA regulatory network was established by analyzing three enriched KEGG pathways significantly correlated with HCC onset and then visualized at CytoScape.
In this work, nine upregulated and nine downregulated DEMs were identified. Functional enrichment analyses showed that these predicted target genes were significantly associated with cancer development. Analysis of three enriched pathways related to the onset of HCC identified 13 and nine target genes for upregulated DEMs and downregulated DEMs, respectively. Subsequently, the miRNA-mRNA regulatory networks were constructed.
In conclusion, miRNA-mRNA regulatory network was established, which will help to understand the mechanism underlying the AFB1-induced onset of HCC.
黄曲霉毒素 B1(AFB1)暴露是引发肝细胞癌(HCC)的关键因素。然而,关于与 AFB1 相关的 HCC 的综合 miRNA-mRNA 调控网络仍然缺乏。本研究旨在鉴定 AFB1 暴露后人原代肝细胞中的 miRNA-mRNA 网络。
使用 GEO2R 从基因表达综合数据库(GEO)中获取的 miRNA 表达数据集 GSE71540,鉴定 AFB1 暴露后差异表达的 miRNA(DEMs)。使用 TargetScan V_7.2、miRDB、PITA、miRanda 和 miRTarBase 鉴定这些 DEMs 的靶基因。在数据库注释、可视化和综合发现(DAVID)中进行基因本体(GO)注释和京都基因与基因组百科全书(KEGG)富集分析。通过分析与 HCC 发生显著相关的三个富集的 KEGG 途径,建立 miRNA-mRNA 调控网络,然后在 Cytoscape 中可视化。
在这项工作中,鉴定了 9 个上调和 9 个下调的 DEMs。功能富集分析表明,这些预测的靶基因与癌症的发生发展显著相关。分析与 HCC 发生相关的三个富集途径,分别鉴定出上调 DEMs 和下调 DEMs 的 13 个和 9 个靶基因。随后,构建了 miRNA-mRNA 调控网络。
总之,建立了 miRNA-mRNA 调控网络,有助于理解 AFB1 诱导 HCC 发生的机制。