Exosome-Mediated Transfer of miR-3613-5p Enhances Doxorubicin Resistance by Suppression of PTEN Expression in Breast Cancer Cells

J Oncol. 2022 Oct 14:2022:9494910. doi: 10.1155/2022/9494910. eCollection 2022.

Abstract

Breast cancer is the most common malignancy among women worldwide, and patients easily develop resistance to the first-line drug doxorubicin. To elucidate the molecular mechanism of drug resistance in breast cancer is imperative. Exosomes mediate the crosstalk between neighboring cells and intercellular communication. Incorporation of miRNAs into exosomes prevents the degradation and facilitates the intercellular communication, which has been indicated in regulation of drug resistance. qRT-PCR revealed that miR-3613-5p is upregulated in drug-resistant breast cancer, and miR-3613-5p exists in exosomes. It is predicted that miR-3613-5p can bind to the tumor suppressor gene PTEN. In this study, our results showed that miR-3613-5p was upregulated in drug-resistant tissue and in exosomes of breast cancer cells resistant to doxorubicin. CCK8, crystal violet staining, and flow cytometry analysis demonstrated that exosome mediated miR-3613-5p transfer and enhanced the resistance to doxorubicin of breast cancer cells. Western blotting showed that miR-3613-5p could target PTEN and regulate the expression of PTEN. Exosome-mediated transfer of miR-3613-5p enhanced the resistance to doxorubicin by inhibition of PTEN in breast cancer cells.