Impact of MiRNAs on Wnt-related gene activity in breast cancer

Breast cancer is the most commonly diagnosed cancer in women. The Wnt pathway is involved in the regulation of cell proliferation, differentiation, survival, and migration. Its disruption may promote the induction of breast cancer and its further development. The aim of the study was to identify micro RNA (miRNAs) that could potentially influence the activity of Wnt-related genes in five types of breast cancer in Polish women. Study included patients with five breast cancer subtypes: 130 luminal A, 96 HER2-positive luminal B, 100 HER2-negative luminal B, 36 non-luminal HER2-positive, 43 triple negative breast cancer (TNBC). Tumor tissue was removed during surgery along with a margin of healthy tissue (control group). Expression profile of Wnt-related genes was assessed with mRNA microarrays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression was conducted with enzyme-linked immunosorbent assay (ELISA). miRNA profiling was carried out with miRNAs microarrays and the miRDB database. Reduced activity of miR-130a could be related to overexpression of CCND1 and GSK3B. Similarly for miR-199a and GSK3B. High activity of miR-2115 could be associated with downregulation of TCF7L2. WNT5 A overexpression may be linked to low levels of miR-497. In addition, study revealed increased levels of APC, DVL3, LEF1 with reduced activity of FZD4 and TCF7L1 in all five subtypes of breast cancer.