###### Abstract  
_Background_: Breast cancer affects over 2 million women yearly. Its early detection allows for successful treatment, which motivates to research factors that enable an accurate diagnosis. miR-125a is one of them, correlating with different types of cancer. For example, the miR-125a level decreases in breast cancer tissues; polymorphisms in the miR-125a encoding gene are related to prostate cancer and the risk of radiotherapy-induced pneumonitis. _Methods_: In this work, we investigated two variants of rs12976445 polymorphism in the context of breast cancer. We analyzed the data of 175 blood samples from breast cancer patients and compared them with the control data from 129 control samples. _Results_: We observed the tendency that in breast cancer cases TT genotype appeared slightly more frequent over CC and CT genotypes (statistically nonsignificant). The TT genotype appeared also to be more frequent among human epidermal growth factor receptor 2 (HER2) positive patients, compared to HER2 negative. In silico modelling showed that the presence of uridine (U) diminished the probability of pri-miR-125a binding to NOVA1 and HNRNPK proteins. We demonstrated that U and C -variants could promote different RNA folding patterns and provoke alternative protein binding. _Conclusions_: U-variant may imply a lower miR-125a expression in breast cancer. microRNA; RNA protein binding; RNA folding; breast cancer; polymorphism +
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One of such potentially useful miRNA marker is miR-125a-the gene is located on chromosome 19, in the proximity of miR-99b and let-7e. This miRNA cluster is situated within the first intron of the transcription unit of sperm acrosomal membrane-associated protein 6 (SPACA6) variant 1 [10]. The genomic DNA sequence located between -3875 bp and -3006 bp from pre-miR-99b drives the expression of SPACA6 gene and its intronic miR-99b/let-7e/miR-125a cluster [10]. miR-125a is involved in the development of various types of cancer, including lung, gastric, and breast cancers [6; 11; 12; 13]. miR-125a functions as an oncomir or a tumour suppressor miRNA depending on the cellular context [6; 14]. In breast cancer tissues, the miR-125a level is decreased when comparing to normal adjacent tissue. Several SNPs have been already described in pri-miR-125a and mature miR-125a: rs41275794 (A/G) and rs12976445 (C/T) SNPs in the pri-miR-125a; rs12975333 (G/T) SNP on the 5' strand and -rs143525573 (A/G) SNP on the 3' strand of mature miR-125a [15; 16; 17]. rs12976445 C and T haplotypes are correlated with cancerous and noncancerous diseases [18; 19]. One of the SNPs in miR-125a, rs12976445, is considerably associated with lymph node metastasis, tumour stage (Classification of Malignant Tumors, TNM), estrogen receptor status, and progesterone receptor status [19]. The TT genotype of rs12976445 significantly increases the risk of mortality in breast cancer patients compared with those carrying the CC genotypes of the SNP [19]. Moreover, patients carrying the TT or CT genotype ofrs12976445 have a higher risk of radiotherapy-induced pneumonitis [20; 21]. The CC-variant of the mentioned SNP has been shown to correlate with higher expression compared with C/T and T/T [20]. Homozygous CC-variant of rs12976445 was shown to increase the risk of prostate cancer [22]. In a study of autoimmune thyroid diseases, it was found that the C allele is significantly increased in [PERSON]'s thyroiditis patients [18]. In the same study, a protecting role of the T allele was suggested to decrease the risk for [PERSON]'s thyroiditis for about 31.6% [18]. Although it has been suggested that SNPs have an impact on miRNA expression and are associated with various diseases, the precise mechanism of the rs12976445 effect on miR-125a processing remains unknown. In vitro and in silico analysis of the SNP and the recognition of proteins interacting with rs12976445 SNP can reveal a detailed picture of the underlying mechanism.