Inhibition of Mir-155 Using Exosomal Delivery of Antagomir Can Up-Regulate Pten in Triple Negative Breast Cancer Publisher Pubmed



J Razaviyan JAVAD ; M Siratisabet MAJID ; A Tafti ALI ; R Hadavi RAZIE ; S Karima SAEED ; M Rajabi Bazl MASOUMEH ; S Mohammadiyeganeh SAMIRA
Source: Endocrine, Metabolic and Immune Disorders - Drug Targets Published:2024

Abstract

Background: 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 nanosized 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. Methods: Bioinformatics analysis of genes related to TNBC revealed that PTEN 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 PTEN was evaluated in MDA-MB-231 cells treated with antagomir-loaded exosomes. Results: Based on the bioinformatics analysis, miR-155 is a potent inhibitor of PTEN. Following treatment with antagomir-loaded exosomes, RT-qPCR showed significantly reduced miR-155 and increased PTEN levels in MDA-MB-231 cells. Conclusion: 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. © 2024 Elsevier B.V., All rights reserved.