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

Javad Razaviyan; Majid Sirati-Sabet; Ali Tafti; Razie Hadavi; Saeed Karima; Masoumeh Rajabibazl; Samira Mohammadi-Yeganeh

doi:10.2174/0118715303289859240214103350

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

Endocr Metab Immune Disord Drug Targets. 2024 Feb 28. doi: 10.2174/0118715303289859240214103350. Online ahead of print.

Authors

Javad Razaviyan¹, Majid Sirati-Sabet¹, Ali Tafti², Razie Hadavi³, Saeed Karima¹, Masoumeh Rajabibazl¹, Samira Mohammadi-Yeganeh^{4

5}

Affiliations

¹ Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Department of Biotechnology and Molecular Medicine, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
³ Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

PMID: 38424419
DOI: 10.2174/0118715303289859240214103350

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 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.

Method: 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.

Keywords: Breast Cancer; Exosome; PTEN; Triple-negative breast cancer; miR-155; therapies..