## 4 Discussion
This protein was not recognized as a possible binding protein to the U-variant. This indicated that RNA processing proteins have a different affinity to C-variant and U-variant potentially modulating the probability of pre-miR-125a RNA maturation. We also predicted the 2D structures of 51 nt sequence with C-/U-variant. We applied the same RNAfold system as [PERSON] et al. [15]. These authors have modelled the 2D structures of rs12976445 allele T, revealing that the rare allele T can neither change the predicted secondary structure nor the predicted \(\Delta\)G [15]. [PERSON] used 1016 nt fragment of RNA, whereas we used RNAfold with 51 nt, revealing two different 2D structures and different hairpin structures in U-variant and C-variant. The shorter sequence used in our study strengthened the obtained results of modelling as in silico methods deal better with shorter sequences. In a later paper, [PERSON] et al. admitted the difference in 2D structure between variants of rs12976445 rare allele T using the same software as previously and the same 1016 nt RNA fragment [40]. For RNAfold-predicted structures we received different models per each variant. C-variants predicted by this tool were either a part of a hairpin loop (as an unpaired nucleotide) or as a base pair near the hairpin loop. On the contrary, U-variants in RNAfold were part of a long unpaired region on the 3' end of the sequence. RNAstructure program predicted 3 models for the C-variant sequence and 2 for the U-variant. In the Figure 3b,c,e structures were identical (except for the SNP in A1.2). Let us notice, that in Figures 2a and 3a are the same structures, and Figure 3c,d models are identical, despite using different predicting tools. Using two computational programs, we revealed the potential differences in RNA-binding proteins between the analyzed C- and U-variant. We found that NOVA1 and HRNPK RNA-binding protein may interact with the C-variant and PTBP1 with the U-variant. Polypyrimidine tract binding protein 1 (PTBP1) binds to mRNA and regulates alternative splicing patterns [43]. In the previous reports, it has been shown that PTBP1 enhances miR-101-guided AGO2 (Argonaute) interaction with MCL1, thereby regulating miR-101-induced apoptosis and cell survival [44]. NOVA1 stimulates miRNA function by different mechanisms that converge on Argonaute proteins, a core component of the miRNA-induced silencing complex (miRRSC). NOVA1 physically interacts with Ago proteins, and control neuronal miRSC function at the level of Ago proteins, with possible implications for the regulation of synapse development and plasticity [35; 45]. Heterogeneous nuclear ribonucleoprotein K (hnRNPK), a ubiquitously occurring RNA-binding protein (RBP), can interact with many nucleic acids and various proteins and is involved in several cellular functions including transcription, translation, splicing, chromatin remodelling, etc. [36]. The limitation of the current study is the number of cases and controls. In the future study, a larger group of breast cancer patients should be analyzed to confirm the tendency of TT genotype association with breast cancer and to test the significance of the observed associations.