Yang Fang, Chen Fengxia, Xu Jin, Guan Xiaoxiang
Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
Oncol Lett. 2016 Apr;11(4):2481-2486. doi: 10.3892/ol.2016.4252. Epub 2016 Feb 19.
Genetic mutation of breast cancer 1 () is one of the most notable factors responsible for a proportion of breast cancer cases. encodes a 1,863-amino acid protein and functions as a negative regulator of tumor growth. Thus, investigation of the underlying mechanisms that regulate gene expression provide further insight into possible targets for breast cancer therapy. Previous studies have demonstrated that the genetic variants in the 3' untranslated region (3'UTR), in addition to the cytosine-phosphate-guanine (CpG) islands in the promoter region, are significantly associated with breast cancer risk; however, the role of single nucleotide polymorphisms (SNPs) in the 3'UTR remains unclear. The present study aimed to investigate the association between SNPs and mRNA expression levels. Bioinformatics analysis demonstrated that 2 SNPs in the 3'UTR (rs12516 and rs8176318 with putative microRNA binding sites) were significantly correlated with mRNA expression in lymphoblastoid cell lines (P=2.55×10-4 and P=8.78×10, respectively). Furthermore, the genotype frequency distribution varied between populations worldwide. In addition, 3 CpG islands and several transcription factor binding sites in the promoter region were established. The identification of such polymorphisms and CpG islands may aid in designing improved therapeutic strategies to treat patients with -associated breast cancer.
乳腺癌1（ ）基因的突变是导致部分乳腺癌病例的最显著因素之一。 编码一种含1863个氨基酸的蛋白质，并作为肿瘤生长的负调节因子发挥作用。因此，对调节 基因表达的潜在机制进行研究，可为乳腺癌治疗的潜在靶点提供进一步的见解。先前的研究表明，除启动子区域的胞嘧啶 - 磷酸 - 鸟嘌呤（CpG）岛外， 3'非翻译区（3'UTR）中的基因变异与乳腺癌风险显著相关；然而，3'UTR中单个核苷酸多态性（SNP）的作用仍不清楚。本研究旨在探讨SNP与 mRNA表达水平之间的关联。生物信息学分析表明，3'UTR中的2个SNP（rs12516和rs8176318，具有假定的微小RNA结合位点）与淋巴母细胞系中的mRNA表达显著相关（分别为P = 2.55×10 - 4和P = 8.78×10）。此外，全球不同人群的基因型频率分布存在差异。另外，在 启动子区域确定了3个CpG岛和几个转录因子结合位点。鉴定这些多态性和CpG岛可能有助于设计更好的治疗策略来治疗与 相关的乳腺癌患者。
