Investigating miR-6880-5p in extracellular vesicle from plasma as a prognostic biomarker in endocrine therapy-treated castration-resistant prostate cancer

Abstract

Background

Advancements in the diagnosis, treatment, and surveillance of castration-resistant prostate cancer (CRPC) have progressed considerably, but a new biomarker that combines existing clinical and pathological data could be useful for a more precise diagnosis and prognosis. Some investigations have found that extracellular vesicle (EV)-derived miRNAs play crucial roles in various types of malignant tumors. The objective of this study was to explore EV miRNA and identify its biologic function as a biomarker for the diagnosis and prognosis of CRPC.

Methods

Plasma samples were collected from five healthy donors (Control, CT) and 17 CRPC patients, categorizing into two groups based on their endocrine treatment response: partial response (PR; n = 10) and progressive disease (PD; n = 7). Candidate extracellular vesicle (EV) miRNAs were identified using miRNA microarray and RT-qPCR. The biological functions of the selected miRNAs were evaluated using the MTT assay, wound healing assay, trans-well assay, and RNA sequencing in CRPC cells after transient miRNA expression.

Results

Microarray analysis revealed a significant downregulation of EV-miR-6880-5p in the PD samples compared to both CT and PR samples (p < 0.01). The expression of EV-miR-6880-5p in CRPC patients was decreased compared with that CT group (p = 0.0336) using RT-qPCR. In the PR group, EV-miR-6880-5p was increased at follow-up compared with the baseline (p = 0.2803), while in the PD group, it decreased at follow-up compared with the baseline samples (p = 0.4356). Furthermore, overexpression of miR-6880-5p hampered cell proliferation, migration, and invasion, downregulated pathways associated with tumor progression, and simultaneously upregulated pathways associated with cell growth and apoptosis in CRPC cells.

Conclusions

EV-miR-6880-5p shows promise as a prognostic biomarker in patients with CRPC. Further, prospective validations are necessary to evaluate the potential of these candidate miRNAs.