Single nucleotide polymorphisms in miRNA binding sites (miR-SNPs) are associated with cancer risk. We assessed the relationship between five miR-SNPs in the 3′ untranslated region (3′-UTR) of RYR3 (rs1044129), KIAA0423 (rs1053667), C14orf101 (rs4901706), GOLGA7 (rs11337), and KRT81 (rs3660) and the risk of breast cancer (BC). The CC genotype of rs3660 located in the 3′-UTR of KRT81 was identified for its association with lower BC risk (odds ratio, 0.093; 95% confidence interval, 0.045–0.193; p = 0.000). Immunnochemical analysis and Renilla luciferase reporter assays indicated that the CC genotype of KRT81 was associated with lower expression of KRT81 (p < 0.05). The subsequently functional analysis showed that knockdown the KRT81 could inhibit proliferation and promote apoptosis of the MDA-MB-231 BC cells (p < 0.05) with monocyte chemotactic protein-1 (MCP-1) deregulation. Meanwhile, KRT81 overexpression could promote the proliferation and inhibit the apoptosis of MCF-7 BC cells (p < 0.05). Our data demonstrated that the KRT81 expressional change modulated by rs3660 miR-SNP could modify the carcinogenesis of BC, thereby KRT81 would be a new target for BC treatment.

中文翻译：

---

在KRT81的3'非翻译区的microRNA结合位点的多态性与乳腺癌有关。

miRNA结合位点（miR-SNP）中的单核苷酸多态性与癌症风险相关。我们评估了RYR3（rs1044129），KIAA0423（rs1053667），C14orf101（rs4901706），GOLGA7（rs11337）和KRT81（rs3660）3'非翻译区（3'-UTR）中的五个miR-SNP与风险之间的关系乳腺癌（BC）。已确定位于KRT81 3'-UTR的rs3660的CC基因型与较低的BC风险相关（优势比，0.093； 95％置信区间，0.045-0.193；p  = 0.000）。免疫化学分析和海肾荧光素酶报告基因检测表明，KRT81的CC基因型与KRT81的较低表达相关（p  <0.05）。随后的功能分析表明，敲除KRT81可以抑制MDA-MB-231 BC细胞的增殖并促进其凋亡（p  <0.05），而单核细胞趋化蛋白1（MCP-1）的失调。同时，KRT81的过表达可以促进MCF-7 BC细胞的增殖并抑制其凋亡（p  <0.05）。我们的数据表明，rs3660 miR-SNP调控的KRT81表达变化可以修饰BC的癌变，因此KRT81将成为BC治疗的新靶点。