Abstract 150P
Background
Difficulties in breast cancer (BC) treatment are associated with the occurrence of metastases at early stages of disease. It is known that ER and PR status may change during metastatic tumor progression. Recent studies have shown that changes in androgen receptor (AR) expression are associated with mammary gland carcinogenesis. Therefore a study of pathways involving these receptors might help understanding mechanisms of BC progression, as the expression of their targets, including their miRNA-targets, can also change.
Methods
The search for miRNAs whose putative promoter regions contain AR, PR or ER binding sites was performed using Biostrings (R Bioconductor package). The level of miRNAs was evaluated by RT-PCR in MCF-7 cells treated for 6, 24, 48 hours with 10 nM or 100 nM of estradiol (E2), progesterone (P4) or testosterone (T). The expression of the miRNAs most sensitive to the action of hormones was analyzed in BC samples (n=94).
Results
15 miRNAs with high expression in the mammary gland were selected to analyze their level in the MCF-7 cells. 5 miRNAs changed 1.3-2 times under the influence of hormones: miRNA-27a (decreased after incubation with T), -190a (increased after incubation with T, decreased after incubation with P4), -190b (increased after incubation with E2), -21 (increased after incubation with T), -193b (increased after incubation with T and E2), -324 (increased after incubation with P4). MiRNA-190a, -190b (lower level in T2-T3 tumors of luminal A), -324, (lower level in T2-T3 tumors of luminal B HER2-positive subtype) were found to be associated with tumor size. The levels of miRNA-193b, -190a decreased in the tissues of patients with lymph node metastases in luminal A. In luminal B HER2-positive BC, the levels of miRNA-190a, -190b, -193b, -21 were significantly lower in the tumor tissues of patients with lymph node metastases. Association with the level of ER expression in luminal B HER2-negative BC was found for miRNA-190b (increase at a higher level of ER).
Conclusions
The study revealed an association between the expression of hormone-sensitive miRNAs (-190a, -190b, -193b, -21, -324) and T stage, N stage, the level of ER expression in some BC subtype.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Russian Science Foundation; grant number: 19-15-00319.
Disclosure
All authors have declared no conflicts of interest.