Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China.
Department of Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China.
DNA Cell Biol. 2020 Oct;39(10):1886-1894. doi: 10.1089/dna.2019.5179. Epub 2020 Jul 15.
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 (rs1044129), (rs1053667), (rs4901706), (rs11337), and (rs3660) and the risk of breast cancer (BC). The CC genotype of rs3660 located in the 3'-UTR of was identified for its association with lower BC risk (odds ratio, 0.093; 95% confidence interval, 0.045-0.193; = 0.000). Immunnochemical analysis and Renilla luciferase reporter assays indicated that the CC genotype of was associated with lower expression of ( < 0.05). The subsequently functional analysis showed that knockdown the could inhibit proliferation and promote apoptosis of the MDA-MB-231 BC cells ( < 0.05) with monocyte chemotactic protein-1 (MCP-1) deregulation. Meanwhile, overexpression could promote the proliferation and inhibit the apoptosis of MCF-7 BC cells ( < 0.05). Our data demonstrated that the expressional change modulated by rs3660 miR-SNP could modify the carcinogenesis of BC, thereby would be a new target for BC treatment.
单核苷酸多态性（SNP）在 miRNA 结合位点（miR-SNPs）中与癌症风险相关。我们评估了位于 3'非翻译区（3'-UTR）中的五个 miR-SNPs（rs1044129、rs1053667、rs4901706、rs11337 和 rs3660）与乳腺癌（BC）风险之间的关系。rs3660 的 CC 基因型位于 3'-UTR 中，与较低的 BC 风险相关（比值比，0.093；95%置信区间，0.045-0.193；=0.000）。免疫化学分析和 Renilla 荧光素酶报告基因检测表明，的 CC 基因型与较低的表达相关（<0.05）。随后的功能分析表明，敲低可抑制 MDA-MB-231 BC 细胞的增殖并促进其凋亡（<0.05），同时伴有单核细胞趋化蛋白-1（MCP-1）失调。此外，过表达可促进 MCF-7 BC 细胞的增殖并抑制其凋亡（<0.05）。我们的数据表明，rs3660miR-SNP 调节的表达变化可修饰 BC 的癌变过程，因此可能成为 BC 治疗的新靶点。
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