Identifying of miR-98-5p/IGF1 axis contributes breast cancer progression using comprehensive bioinformatic analyses methods and experiments validation

Abstract

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.

Keywords: Breast cancer; IGF1; has-miR-98-5p; mRNA; miRNA.