The role of miR-223 in breast cancer; an integrated analysis

Background: Breast cancer (BRCA) is the most common and leading cause of cancer-related death in women. MicroRNAs (miRNAs) are short non-coding RNA fragments that play a role in regulating gene expression including the cancer-related pathways. Although dysregulation of miR-223 has been demonstrated in recent studies to have prognostic value in various cancers, its diagnostic and prognostic role in BRCA remains unknown.

Methods: The expression and the prognostic value of miR-223 were evaluated using the TCGA data and verified by qRT-PCR. Subsequently, potential oncogenic targets of miR-223 were identified by using three different miRNA target prediction tools and the GEPIA database. In addition to these databases, protein-protein interaction network, molecular functions, prognostic value, and the expression level of miR-223 targets were included by using several other bioinformatics tools and databases; such as, UALCAN, GeneMANIA and Metascape.

Results: The bioinformatic results demonstrated that miR-223 downregulated in BRCA and associated with poor prognosis of patients. In vitro experiments validated that miR-223 significantly downregulated in BRCA cells, MCF-7, SK-BR3, MDA-MB-231 and HCC1500, compared to normal breast cell line hTERT-HME1. Furthermore, ANLN, DYNLT1, LRRC59, SLC12A8 and TPM3 genes were identified as the potential oncogenic target genes of miR-223 based on their expression and prognosis in BRCA. Additionally, protein-protein interaction network of these target genes was mainly enriched in dynein intermediate chain binding, cell division, regulation of cell cycle process, and positive regulation of cellular component biogenesis.

Conclusions: The results suggests that miR-223 and its targets, ANLN, DYNLT1, LRRC59, SLC12A8 and TPM3, might be reliable potential prognostic biomarkers in BRCA patients.