Petrovic Nina, Davidovic Radoslav, Bajic Vladan, Obradovic Milan, Isenovic R Esma
Cancer Biomark. 2017;19(2):119-128. doi: 10.3233/CBM-160319.
Breast cancer (BC) is a heterogeneous disease in an urgent need for developing novel research, classification, and therapy approaches. Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins are well described tumor suppressors with great potential to be the subjects of different therapies. MicroRNAs (miRNAs) are genetic elements that might be used to solve the complex BC puzzle. BRCA1 was described to be the target of up to 100 miRNAs. BRCA1 may directly repress miR-155 activity. In addition, miR-15/107/182-mediated downregulation of BRCA1 interrupt DNA repair and may change the course of BC therapy. miR-146a and miR-146-5p silencing BRCA1 may trigger formation of triple-negative and basal-like sporadic BC cases. miR-182 might effect the therapy outcome. miR-21 targeted therapy might be useful for the treatment of BRCA2 mutation carriers. miR-342 overexpression and the absence of functional BRCA1 gene might cause synthetic lethality, which might be used as a base for future therapies. The present review discusses the latest data from studies that focus on the complex network of miRNAs and BRCA1/2 related BCs, which might be important for improving the therapy within the patients with triple-negative BC (TNBC) and basal-like BC, and for understanding the formation of TNBC.
乳腺癌（BC）是一种异质性疾病，迫切需要开发新的研究、分类和治疗方法。乳腺癌1（BRCA1）和乳腺癌2（BRCA2）蛋白是已被充分描述的肿瘤抑制因子，极有可能成为不同治疗方法的研究对象。微小RNA（miRNA）是一类遗传元件，可能有助于解开复杂的乳腺癌谜团。据报道，BRCA1是多达100种miRNA的作用靶点。BRCA1可能直接抑制miR-155的活性。此外，miR-15/107/182介导的BRCA1下调会干扰DNA修复，并可能改变乳腺癌的治疗进程。miR-146a和miR-146-5p沉默BRCA1可能引发三阴性和基底样散发性乳腺癌病例的形成。miR-182可能影响治疗效果。miR-21靶向治疗可能对BRCA2突变携带者的治疗有用。miR-342的过表达和功能性BRCA1基因的缺失可能导致合成致死性，这可能成为未来治疗的基础。本综述讨论了聚焦于miRNA与BRCA1/2相关乳腺癌复杂网络的研究的最新数据，这些数据可能对改善三阴性乳腺癌（TNBC）和基底样乳腺癌患者的治疗以及理解TNBC的形成具有重要意义。
