miR-638靶向BRCA1调控三阴性乳腺癌的作用机制研究

乳腺癌是女性最常见的恶性肿瘤之一，其中三阴性乳腺癌（TNBC）侵袭性强、预后差，与其他类型的乳腺癌相比，缺乏较有效的治疗方法与靶向药物。MiRNAs是近期肿瘤研究的前沿热点之一，广泛参与细胞各种生理、病理过程的调节。本项目前期通过基因芯片检测了7对三阴性乳腺癌组织中miRNA的表达谱，发现了miR-638在TNBC组织中表达上调，随后使用软件预测发现乳腺癌1号基因（BRCA1）是miR-638的靶基因之一，并通过实验初步验证，因此推测miR-638靶向BRCA1的机制可能是调控TNBC发生的重要途径之一。本项目拟分析200对TNBC组织中miR-638的表达，研究其表达与TNBC发生的相关性，并通过体外细胞功能实验、裸鼠模型、miR-638的自身表达调控以及与RNA结合蛋白的共同作用，来研究其在TNBC中的作用及其机制，为三阴性乳腺癌的靶向治疗提供新的思路。

Breast cancer is one of the most prevalent and serious malignancies affecting women worldwide. Triple negative breast cancer (TNBC) is considered as a kind of disease with aggressive behaviors, poor prognosis and easy local recurrence. Compared with ER-positive and HER-2 positive breast cancer, TNBC is lack of effective treatment and target therapeutic drug. MiRNAs play critical roles in lots of biological and physiological processes. In this study, we used microRNA microarray to detect the changes of miRNAs expression in 7 pairs of TNBC tissues. The results showed that miR-638 was up-regulated significantly which was authenticated by Northern blot as well. Subsequently, we applied TargetScan software to predict the target genes of miR-638. BRCA1 was authenticated as one of the target genes of miR-638 by applying the luciferase reporter assay and Western blot analysis. All data indicated that effect of miR-638 on TNBC might be achieved by targeting BRCA1. We will further study the expression of miR-638 and BRCA1 in 200 samples and focused on their correlation with clinicopathological characteristics of breast cancer. Subsequent functional analysis could be used to explore the mechanisum involved in the TNBC occurrence. In summary, the up-regulated expression of miR-638 may be employed as a potential biomarker of TNBC and improve the therapy and prognosis.