## 4 Discussion  
The analysis of our results concerning rs12976445 SNP in miR-125a revealed that the TT genotype was slightly more frequent in breast cancer patients and HER2 positive patients. Our study revealed only a tendency, and we obtained \(p\)-values above 0.05. One reason for this is the participation of miR-125a with numerous other factors in the development of breast cancer. The correlation of such multigenic diseases with single SNP requires a greater number of individuals and controls. Our findings suggested that rs12976445 has the potential to be a predictive biomarker for cancer risk, but a meta-analysis of a greater number of cases is required. Several studies have described the association of rs12976445 genotypes TT, CT, and CC in miR-125a with cancer and other diseases. In the Chinese study of [PERSON] et al. TT genotype has been significantly related to increased risk of mortality in breast cancer patients compared with those carrying the CC genotypes [19]. miR-125a rs12976445 was significantly associated with survival in codominant, recessive, and dominant models. However, only an association under the codominant model remained significant after adjustment for lymph node metastasis, TNM stage, estrogen receptor, and progesterone receptor [19]. It has been shown in previous studies that the miR-125a level is decreased in breast cancer [32; 33; 34], however, the level of miR-125a-5p is significantly higher in younger patients than in the older ones [38]. It has been shown that SNPs located in miR-125a are associated with breast cancer tumorigenesis [39] and rs12976445 SNP in miR-125a may serve as a prognostic biomarker for breast cancer [19]. Although rs12976445 is associated with breast and prostate cancer, the impact of this SNP has been rarely studied in a functional assay. The prominent study of the effect of rs12976445 on miR-125a expression was evaluated in the context of recurrent pregnancy loss [40; 15]. In embryonic kidney cells, HEK293T miR-125a expression level of C haplotype was nearly four-fold higher than T haplotype [40; 15]. The question remained how the rs12976445 genotype impacts the miR-125a level. In the previous studies, rs12976445 SNP in miR-125a has been associated with the risk of pneumonitis [20]. The expression level of miR-125a mRNA has been significantly downregulated in the CT and TT groups, and CC genotype samples demonstrated upregulated miR-125a expression [20; 21]. Rs12976445 polymorphism, also associated with the risk of diabetic nephropathy, showed that the expression levels of miR-125a were approximately three times lower in patients carrying TT and CT than in the CC [41]. Other studies showed that concomitantly with miR-125a the expression of miR-205 in breast cancer is also downregulated due to SNP variations in the miR-205 sequence [42]. Studies in various cell lines identified the differential expression of miR-205 in breast cancer cell lines in correlation with the missing number of AGC repeats [42]. Herein, we decided to analyze the association of rs12976445 genotypes with breast cancer. Moreover, we performed computational research to find potential protein interacting with the SNP region and to predict and compare the 2D structure of C-/U-variant sequence. In both cases, we used two independent tools, RBPmap and ATtRACT for RNA binding protein (RBP) search, and RNAstructure and RNAfold programs to build 2D models. We observed different RBP mapped to C- and U-variants of the sequence. Both programs that we used indicated the interaction between U-variant and PTBP1 protein. In C-variant, NOVA1 protein appears in the results obtained from both ATtRACT and RBPmap. It should be underlined that NOVA1 was found only in the C-variant sequence, whereas connection with PTBP1 protein was established in U- and C-variant by RBPmap program. Another interesting fact was the appearance of HNRNPK protein in the results for C-variant obtained from RBPmap for low and medium stringency level of the algorithm search criteria.