Background

Breast cancer (BC) is a huge health threat for women worldwide. Although numerous microRNAs (miRNA) have been found to be aberrantly expressed in BC, the construction of a comprehensive miRNA-messenger RNA (mRNA) network is still needed.

Methods

Limma package was used to identify differentially expressed miRNAs (DEMs) in microarray datasets downloaded from GEO database. Genes targeted by DEMs were analyzed using mirTarBase. Gene Ontology and pathway enrichment analysis for these genes were performed at DAVID. Expression correlations of DEMs and target genes were analyzed at ENCORI. Based on these results, a miRNA-mRNA regulatory network was constructed.

Results

A total of 17 overlapping DEMs were identified at these two microarray datasets. Expression of DEMs in BC tissues compared with normal tissues were further validated by ENCORI. By utilizing miRTarBase, a total of 167 target genes for DEMs were obtained. 10 hub genes (AKT1, MYC, VEGFA, CCND1, PTEN, IL6, CASP3, KRAS, IGF1, ESR1) were identified. Through analyzing the effects of hub genes on overall survival of BC patients and their expression correlation with miRNAs, we found hsa-miR-98-5p/IGF1 axis may play a crucial role in BC progression. The connections of hsa-miR-98-5p and IGF1 were further validated by luciferase activity reporter assay and functional assays.

Conclusions

In this work, a miRNA-mRNA network related to BC progression was built, and identified one important miRNA-mRNA axis in BC.

中文翻译：

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使用全面的生物信息学分析方法和实验验证，鉴定miR-98-5p / IGF1轴有助于乳腺癌的进展。

背景

乳腺癌（BC）对全世界的妇女来说都是巨大的健康威胁。尽管已经发现许多微RNA（miRNA）在BC中异常表达，但是仍然需要构建全面的miRNA信使RNA（mRNA）网络。

方法

Limma软件包用于识别从GEO数据库下载的微阵列数据集中的差异表达的miRNA（DEM）。使用mirTarBase分析了DEM靶向的基因。这些基因的基因本体论和途径富集分析在DAVID进行。在ENCORI分析DEM和靶基因的表达相关性。基于这些结果，构建了miRNA-mRNA调控网络。

结果

在这两个微阵列数据集中共鉴定出17个重叠的DEM。ENCORI进一步验证了与正常组织相比，BC组织中DEM的表达。通过使用miRTarBase，共获得167个DEM靶基因。鉴定了10个中枢基因（AKT1，MYC，VEGFA，CCND1，PTEN，IL6，CASP3，KRAS，IGF1，ESR1）。通过分析中枢基因对BC患者总体生存的影响及其与miRNA的表达相关性，我们发现hsa-miR-98-5p / IGF1轴可能在BC进程中起关键作用。hsa-miR-98-5p和IGF1的连接通过萤光素酶活性报告基因测定和功能测定进一步验证。

结论

在这项工作中，建立了与BC进程相关的miRNA-mRNA网络，并确定了BC中一个重要的miRNA-mRNA轴。