This month’s featured article is from the lab of Xiaoxiang Guan of Nanjing University in Nanjing, China. The article was published in the January 2017 issue of the journal Molecular Medicine Reports.
This study focused on whether miRNAs have an effect on androgen receptor (AR) expression during breast cancer. Much attention has been paid to the estrogen receptor in breast cancer, but the authors note that the AR is commonly expressed in invasive breast cancers, occurring in over 70% of cases. While the estrogen receptor has been characterized as oncogenic, the AR is often thought of as being protective.
The authors addressed miRNA regulation of AR expression by testing miRNA expression in AR-positive and AR-negative breast cancer cell lines. They profiled miRNAs in theses samples using Phalanx Biotech’s Human miRNA OneArray Microarray. They found 52 up-regulated and 101 down-regulated miRNAs in AR-positive cell lines compared to AR-negative cell lines. The 25 miRNAs with the largest fold changes are shown in the heat map above.
Next, the authors took a systems biology approach to look at the signaling pathways and biological processes affected by the differentially expressed miRNAs. Using miRNA target prediction tools, they identified over 5,000 genes targeted by the differentially expressed miRNAs. This gene list was then subject to gene ontology and pathway enrichment analysis to identify pathways and processes downstream of the miRNAs. Interestingly, numerous components of pathways involved in tumor cell proliferation and invasion were enriched, for example in the VEGF and mTOR signaling pathways. These results suggest that the AR may regulate the pathways through up- or down-regulation of the miRNAs identified in the present study.
In summary, the authors identified differentially expressed miRNAs in AR-positive and AR-negative breast cancer cell lines. These miRNAs are at the heart of the AR’s role in breast cancer. The genes downstream of these miRNAs revealed an interaction between AR expression and the VEGF and mTOR signaling pathways; however, further work is required to improve the understanding of the link between the AR and these signaling pathways.
Reference
Shi Y et al. Differential microRNA expression is associated with androgen receptor expression in breast cancer (2017). Mol Med Rep 15(1):29-36.