Breast cancer is the most commonly diagnosed cancer among women. Difficulties in treating breast cancer are associated with the occurrence of metastases at early stages of disease, leading to its further progression. Recent studies have shown that changes in androgen receptor (AR) and microRNAs’ expressions are associated with mammary gland carcinogenesis, in particular, with the formation of metastases. Thus, to identify novel metastatic markers, we evaluated the expression levels of AR; miR-185 and miR-205, both of which have been confirmed to target AR; and miR-21, transcription of which is regulated by AR, in breast cancer samples (n=89). Here, we show that the molecular subtypes of breast cancer differ in the expression profiles of AR and AR-associated microRNAs. In addition, the expression of AR and these microRNAs may depend on the expression of PR, ER, and HER2 receptors. Our results show that the possibility of using AR and microRNAs as markers depends on the tumor subtype: a decrease in AR expression may be the marker for the presence of lymph node metastases in patients with HER2-positive subtypes of breast cancer, and disturbance of miR-205, miR-185, and miR-21 expressions may be the marker in patients with a luminal B HER2-positive subtype. Cases with metastases in this type of breast cancer are characterized by a higher level of miR-205 and a lower level of miR-185 and miR-21 in tumor tissues compared to nonmetastatic cases. A decrease in the miR-185 level is also associated with lymph node metastasis in luminal B HER2-negative breast cancer. Thus, the expression levels of AR, miR-185, miR-205, and miR-21 can serve as markers to predict cancer spread to the lymph node in luminal B- and HER2-positive subtypes of breast cancer.

Smoking is the main risk factor for lung cancer, mainly due to presence of nitrosamines and polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BP) in tobacco smoke composition. The genotoxic effect of BP is based on the high DNA-binding ability of its metabolites, while the epigenetic effects are mediated by a change in the expression of cancer related genes or regulatory RNAs. It has been shown that women have a higher risk to develop lung cancer upon smoking rather than men. We hypothesized that crosstalk between signaling pathways activated by BP and estrogens could underlie the sex-dependent differences in miRNAs expression. To test this hypothesis, male and female rats were subjected to short-term or long-term BP exposure. Using in silico analysis, miRNAs containing the ER- and AhR-binding sites in the promoters of the genes (or host genes) were selected. During chronic exposure of BP the expression of miR-22-3p, -29a-3p, -126a-3p, -193b-5p in the lungs of male rats were significantly increased, while the level of miRNA-483-3p were decreased. Expression of miRNA-483-3p was up-regulated during chronic BP exposure in the lungs of female rats and the levels of other studied miRNAs were unchanged. In turn, changes in the expression of miRNAs were followed by changes in the expression of their target genes, including PTEN, EMP2, IGF1, ITGA6, SLC34A2, and the observed changes in female and male rat lungs were varied. Thus, our results suggest that sex-dependent epigenetic effects of BP may be based on different expression of AhR- and ER- regulated miRNAs.