Hussen Bashdar Mahmud, Abdullah Khozga Hazhar, Abdullah Snur Rasool, Majeed Nasik Mahmood, Mohamadtahr Sayran, Rasul Mohammed Fatih, Dong Peixin, Taheri Mohammad, Samsami Majid
Department of Biomedical Sciences, College of Science, Cihan University-Erbil, Kurdistan Region, 44001, Iraq.
Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil, Iraq.
Noncoding RNA Res. 2023 Sep 28;8(4):645-660. doi: 10.1016/j.ncrna.2023.09.003. eCollection 2023 Dec.
Brain metastases in breast cancer (BC) patients are often associated with a poor prognosis. Recent studies have uncovered the critical roles of miRNAs in the initiation and progression of BC brain metastasis, highlighting the disease's underlying molecular pathways. miRNA-181c, miRNA-10b, and miRNA-21, for example, are all overexpressed in BC patients. It has been shown that these three miRNAs help tumors grow and metastasize by targeting genes that control how cells work. On the other hand, miRNA-26b5p, miRNA-7, and miRNA-1013p are all downregulated in BC brain metastasis patients. They act as tumor suppressors by controlling the expression of genes related to cell adhesion, angiogenesis, and invasion. Therapeutic miRNA targeting has considerable promise in treating BC brain metastases. Several strategies have been proposed to modulate miRNA expression, including miRNA-Mimics, antagomirs, and small molecule inhibitors of miRNA biogenesis. This review discusses the aberrant expression of miRNAs and metastatic pathways that lead to the spread of BC cells to the brain. It also explores miRNA therapeutic target molecular mechanisms and BC brain metastasis challenges with advanced strategies. The targeting of certain miRNAs opens a new door for the development of novel therapeutic approaches for this devastating disease.
乳腺癌（BC）患者发生脑转移通常预后较差。最近的研究揭示了微小RNA（miRNA）在BC脑转移发生和发展中的关键作用，突显了该疾病潜在的分子途径。例如，miRNA - 181c、miRNA - 10b和miRNA - 21在BC患者中均过度表达。研究表明，这三种miRNA通过靶向控制细胞功能的基因来帮助肿瘤生长和转移。另一方面，miRNA - 26b5p、miRNA - 7和miRNA - 1013p在BC脑转移患者中均下调。它们通过控制与细胞黏附、血管生成和侵袭相关基因的表达发挥肿瘤抑制作用。靶向治疗性miRNA在治疗BC脑转移方面具有巨大潜力。已经提出了几种调节miRNA表达的策略，包括miRNA模拟物、抗miRNA寡核苷酸和miRNA生物合成的小分子抑制剂。本综述讨论了导致BC细胞扩散至脑的miRNA异常表达和转移途径。还探讨了miRNA治疗靶点的分子机制以及先进策略面临的BC脑转移挑战。针对某些miRNA的靶向治疗为这种毁灭性疾病开发新的治疗方法打开了一扇新的大门。
