LAUSR

OBJECTIVE Breast cancer (BC) is the most common type of cancer diagnosed in women. Since BC has heterogeneous molecular structure a common treatment strategy for BC is not available and most of the patients develop resistance through the course of treatment. Therefore, alternative medicine resources as new treatment options are determined to be used for the treatment of BC. Usnic acid (UA) that is one of the secondary metabolites of lichens has been used for different purposes in the field of medicine and its anti-proliferative effect has been mainly shown in some of the cancer types, which makes it a potential treatment molecule. METHODS In this study, UA was isolated from the lichens and determination of anti-proliferative effect in BC cells (MDA-MB-231, MCF-7, BT-474) was performed by MTT analysis. Cells treated with the effective concentration of UA were conducted to microarray analysis to profile UA-responsive miRNAs. After bioinformatics analysis cell specific miRNAs responsive to UA were identified. Their targets and the pathways they are taking part in were determined by using a miRNA target prediction tool. RESULTS Microarray experiments showed that 67 miRNAs were specifically responsive to UA in MDA-MB-231 cells while it was 15 for BT-474 and 8 for MCF-7 cells. The targets of the miRNAs were found to be enriched commonly in Hedgehog signaling pathway. TGF-Beta, MAPK and apoptosis pathways were also the prominent ones according to enrichment analysis. CONCLUSION The pathway enrichment analysis results conducted with the UA responsive miRNAs together with the anti-proliferative effects of UA may make UA as one of the potential alternative therapeutics for treatment of BC. This study is the first study in the literature aiming to find out the molecular mechanism of UA at miRNA level by revealing the differentially expressed miRNAs, their targets and the molecular pathways that may have roles in the BC.