Mirabbasi Razieh, Ebrahimi Seyed Omar, Tavakoli Fatemeh, Reiisi Somayeh
Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran.
3 Biotech. 2023 Nov;13(11):349. doi: 10.1007/s13205-023-03765-y. Epub 2023 Sep 29.
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 ( = 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.
本研究旨在探讨miR-3117-3p种子区域中的rs12402181变体如何影响miRNA加工以及与靶序列的结合能力和乳腺癌易感性。为了研究rs12402181多态性在乳腺癌中的作用，对血液样本进行检测，以研究miR-3117中的基因变体与乳腺癌易感性之间的可能关联。使用PCR-RFLP对miR-3117基因变体进行基因分型。将具有GG或AA基因型的前体miR-3117及其侧翼区域的部分片段插入pEGFPN1表达载体，随后进行qPCR，以评估SNP对miR-3117-3p表达水平和功能的影响。通过MTT和伤口愈合试验研究细胞增殖和迁移特性。利用网络服务器数据库进一步研究miRNA功能的潜在变化。乳腺癌患者和健康对照的基因型频率研究表明，rs12402181多态性（G>A）与乳腺癌易感性呈负相关（P=0.03，OR=0.551）。该变异等位基因导致成熟miR-3117产量增加，并降低MCF7和T47D细胞的增殖和迁移。这些发现表明，miR-3117-3p中的A等位基因影响miRNA的加工，导致miRNA成熟形式增加，从而对肿瘤发展和迁移产生负调控作用。
在线版本包含可在10.1007/s13205-023-03765-y获取的补充材料。
