miRNAs in the box – potential diagnostic role for extracellular vesicle-packaged miRNA in breast cancer

Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. Researchers at the University of Calabria examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in the researchers systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. These findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.

Characterization of circulating extracellular vesicles (EVs) isolated from sera of
healthy subjects and breast cancer patients

(A). Schematic illustration of the study design. Circulating EVs were purified from serum samples of healthy subjects (C) and breast cancer patients (BC) by ExoQuick precipitation system. (B). Representative transmission electron microscopy (TEM) images of EVs isolated from serum of healthy subjects and breast cancer patients. Scale bar, 200 nm. (C). Upper panel, Representative size distribution profiles and concentration of serum EVs measured by nanoparticle tracking analysis (NTA). Lower panel, the table shows the average values for particle concentration and size from NTA results of the entire sample of specimens. (D). Immunoblot analysis showing expression of the EV canonical markers Tsg101, CD9, CD81 in equal amounts of EV lysates. The specificity of EVs isolation was confirmed using the endoplasmic reticulum marker Calnexin. +, MCF-7 breast cancer cell lysates were used as positive control.

Giordano C, Accattatis FM, Gelsomino L, Del Console P, Győrffy B, Giuliano M, Veneziani BM, Arpino G, De Angelis C, De Placido P, Pietroluongo E, Zinno F, Bonofiglio D, Andò S, Barone I, Catalano S. (2023) miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer. Int J Mol Sci 24(21):15695. [article]

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