Novel polymorphism rs12402181 in the mature sequence of hsa-miR-3117-3p has a protective effect against breast cancer...

The current study aimed to investigate how the rs12402181 variant in the miR-3117-3p seed region affects miRNA processing and binding ability to the target sequences and breast cancer susceptibility. To study the role of rs12402181 polymorphism in breast cancer, blood samples were examined to investigate the possible association between the genetic variant in the miR-3117 and breast cancer susceptibility. The miR-3117 gene variant was genotyped using PCR-RFLP. The pre-miR-3117 and parts of the flanking region with GG or AA genotype were inserted into a pEGFPN1 expression vector and followed by qPCR to evaluate the effect of SNP on miR-3117-3p expression levels and function. Cell proliferation and migration properties investigated by MTT and wound healing assay. Web server databases were used for further investigation of potential changes in miRNA function. Genotype frequency study in breast cancer patients and healthy controls showed that rs12402181 polymorphism (G > A) is inversely associated with susceptibility to breast cancer (P = 0.03, OR 0.551). The variant allele led to increased production of mature miR-3117 and reduced cell proliferation and migration in MCF7 and T47D cells. These findings suggest that A allele in miR-3117-3p affects the processing of miRNA, causing an increase in the miRNA mature form which can negatively regulate tumor development and migration.

The online version contains supplementary material available at 10.1007/s13205-023-03765-y.