Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Biotechnology and Molecular Medicine, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
Endocr Metab Immune Disord Drug Targets. 2024;24(14):1664-1676. doi: 10.2174/0118715303289859240214103350.
The most aggressive form of breast cancer (BC) is Triple-Negative BC (TNBC), with the poorest prognosis, accounting for nearly 15% of all cases. Since there is no effective treatment, novel strategies, especially targeted therapies, are essential to treat TNBC. Exosomes are nano-sized microvesicles derived from cells and transport various intracellular cargoes, including microRNAs (miRNAs). MiRNAs, small non-coding RNA, are an influential factor in the development of cancerous transformations in cells.
Bioinformatics analysis of genes related to TNBC revealed that plays a crucial role in the disease. Relative expression of this gene was analyzed with RT-qPCR in 14 TNBC clinical samples. Electroporation was used to load miRNA antagomir into exosomes extracted from the conditioned medium. Then, the expression of miR-155 and was evaluated in MDA-MB-231 cells treated with antagomir-loaded exosomes.
Based on the bioinformatics analysis, miR-155 is a potent inhibitor of . Following treatment with antagomir-loaded exosomes, RT-qPCR showed significantly reduced miR- 155 and increased levels in MDA-MB-231 cells.
Based on the results of this study, exosomes can be effectively used as a cargo of oligonucleotides like miRNA mimics and antagomirs in targeted therapies.
最具侵袭性的乳腺癌（BC）是三阴性乳腺癌（TNBC），预后最差，占所有病例的近 15%。由于没有有效的治疗方法，因此需要新的策略，尤其是靶向治疗来治疗 TNBC。外泌体是源自细胞的纳米级微泡，可运输各种细胞内物质，包括 microRNAs（miRNAs）。miRNAs 是一种小的非编码 RNA，是细胞癌变发展的一个重要因素。
通过对与 TNBC 相关的基因进行生物信息学分析，发现 在疾病中起关键作用。使用 RT-qPCR 在 14 个 TNBC 临床样本中分析该基因的相对表达。使用电穿孔将 miRNA 拮抗剂加载到从条件培养基中提取的外泌体中。然后，评估用载有拮抗剂的外泌体处理的 MDA-MB-231 细胞中 miR-155 和 的表达。
基于生物信息学分析，miR-155 是 的有效抑制剂。用载有拮抗剂的外泌体处理后，RT-qPCR 显示 MDA-MB-231 细胞中 miR-155 明显减少， 水平升高。
基于本研究的结果，外泌体可有效地用作像 miRNA 模拟物和拮抗剂等寡核苷酸的载体，用于靶向治疗。
