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Open AccessArticle

In Vitro and in Silico Analysis of miR-125a with rs12976445 Polymorphism in Breast Cancer Patients

1
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Swiecickiego 6, 60-781 Poznan, Poland
2
Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
3
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland
4
Department of Surgery, Chair and Clinic of Oncology Poznan University of Medical Sciences, Szamarzewskiego 82/84, 61-001 Poznan, Poland
*
Authors to whom correspondence should be addressed.
Appl. Sci. 2020, 10(20), 7275; https://doi.org/10.3390/app10207275
Received: 23 September 2020 / Revised: 14 October 2020 / Accepted: 15 October 2020 / Published: 17 October 2020
(This article belongs to the Special Issue Applications of Nucleic Acids in Chemistry and Biology)
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. View Full-Text
Keywords: microRNA; RNA protein binding; RNA folding; breast cancer; polymorphism microRNA; RNA protein binding; RNA folding; breast cancer; polymorphism
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Lehmann, T.P.; Miskiewicz, J.; Szostak, N.; Szachniuk, M.; Grodecka-Gazdecka, S.; Jagodziński, P.P. In Vitro and in Silico Analysis of miR-125a with rs12976445 Polymorphism in Breast Cancer Patients. Appl. Sci. 2020, 10, 7275.

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