Inhibition of MiR-155 Using Exosomal Delivery of Antagomir Can Up-Regulate PTEN in Triple Negative Breast Cancer

• Published in: Endocrine, metabolic & immune disorders drug targets Vol. 24; no. 14; p. 1664
• Main Authors: Razaviyan, Javad, Sirati-Sabet, Majid, Tafti, Ali, Hadavi, Razie, Karima, Saeed, Rajabibazl, Masoumeh, Mohammadi-Yeganeh, Samira
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-01-2024
• Subjects: Cell Line, Tumor; Exosomes - genetics; Exosomes - metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Up-Regulation; PTEN; therapies; triple-negative breast cancer; Breast cancer; exosome; miR-155
• ISSN: 2212-3873
• 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.