In-silico analysis to investigate altrations in the secondary structure of miR-۳۱۸۸ due to single nucleotide polymorphism

Background and Aim: Introduction Breast cancer (BC) is known as the most frequently identified cancers in women. Age progression as well as being exposed to endogenous estrogen due to reproductive factors are some of the risk-increasing causes behind BC. Women aged ۳۰ are prone to breast cancer ۱ in ۲۵۰ in the next ۱۰ years, whereas this ratio is ۱ in ۲۷ for women aged >۷۰. microRNAs are endogenous, small, and non-coding RNAs with ۲۱-۲۵ nucleotides. They have an important role in gene expression regulation, most of which have degradation and translational repression effect on mRNA by interacting with its ۳' untranslated region (۳'UTR). single nucleotide polymorphism (SNP) is a type of genetic variation which occurs every ~۲۰۰ bases. several studies have shown the effect of SNPs on miRNA genes, target sites, and subsequently their function. In this study, we employed bioinformatic analysis to evaluate the impact of SNPs on miRNA secondary structure. For this purpose, we calculated the minimum free energy (MFE) of miR-۳۱۸۸ and rs۵۵۲۸۲۷۳۶۸ and rs۷۵۷۴۵۲۳۵۳.Methods: Method In order to validate the expression profile of miR-۳۱۸۸ in breast cancer,“miRCancer” database was employed. “miRbase” webserver was used to obtain the sequence of the microRNA. To visualize the molecular interaction network of miR-۳۱۸۸ and its targets,“miRTargetLinkHuman” webserver was used. Investigation of the effect of this variant on stem-loop structure and determination of the minimum free energy (MFE) of the polymorphic and non-polymorphic variants were conducted using “ViennaRNA” web service.Results: Result While the MFE of the non-polymorphic sequence of mir-۳۱۸۸ was -۴۸.۶۰ kcal/mol, the MFE for rs۵۵۲۸۲۷۳۶۸ and rs۷۵۷۴۵۲۳۵۳ was -۴۷.۰۰ and -۴۷.۷۰ kcal/mol, respectively.Conclusion: Discussion Many studies have shown that miR-۳۱۸۸ plays a regulatory role in breast cancer progression by affecting the p۳۸ MAPK signaling pathway. Therefore, we conducted a bioinformatic study to investigate the impact of SNPs (rs۵۵۲۸۲۷۳۶۸ and rs۷۵۷۴۵۲۳۵۳) on miR-۳۱۸۸ secondary structure. The MFE of these two given SNPs were compared to the non-polymorphic miRNA. Considering the difference found between the MEF of SNPs and the non-polymorphic miR-۳۱۸۸, it can be concluded that SNPs can affect the secondary structure of miR-۳۱۸۸.

Keywords:

breast cancer , single nucleotide polymorphism , bioinformatic