<p>Functional Implication of Exosomal miR-217 and miR-23b-3p in the Progression of Prostate Cancer</p>

Abstract

Objective The microRNA expression profile of plasma exosomes in prostate cancer (PCa) is of critical importance in the disease exploration. This study aimed to explore the clinical application of exosomal miRNAs as biomarkers for PCa. Methods Exosome-like vesicles of PCa patients and healthy controls were purified by differential centrifugation. The purified vesicles within the ranges of 50 and 100 nm were classified as exosomes according to the results of transmission electron microscopy and Western blot. Both, in vitro and in vivo, validations were performed by small RNA sequencing, CCK8, RT-qPCR, flow cytometry, Western blot, transwell and immunofluorescent staining assays. Results High-throughput sequencing identified that 94 miRNAs were differentially expressed in PCa patients in comparison with healthy controls ( P <0.01; fold change ≥2). Among them, 64 miRNAs were upregulated, and 30 miRNAs were downregulated. In comparison to the healthy controls, the expression levels of miR-217 were significantly upregulated, while miR-23b-3p were significantly downregulated in the exosomes and serum collected from PCa patients. Both, in vitro and in vivo, studies revealed that exosomes secreted by PCa cells with up-regulated miR-217 levels promoted cell proliferation and invasion; meanwhile, the exosomes with up-regulated miR-23b-3p levels inhibited cell proliferation and invasion. The epithelial–mesenchymal transition process may have been involved in the above-mentioned regulation. Conclusion This study identified the dysregulated expression of exosomal miRNAs in PCa patients, including miR-217 and miR-23b-3p, by validating their function on proliferation and invasion in PCa cells. This regulation may have been affected by the epithelial–mesenchymal transition process, suggesting that they can be used as potential targets in the diagnosis and treatment of PCa.

MicroRNA‑23b‑3p targets non‑SMC condensing I complex subunit G to promote proliferation and inhibit apoptosis of colorectal cancer cells via regulation of the PI3K/AKT signaling pathway

“…In the present study, miRNAs upstream of NCAPG were predicted via bioinformatics analysis, and miR-23b-3p was selected as the candidate miRNA. miR-23b-3p is known to be an important modulator of cellular physiology, and has been strongly associated with cancer development ( 14 ); In fact, the expression levels of miR-23b-3p were reported to be downregulated in cervical ( 25 ), lung ( 26 ) and prostate cancer ( 27 ). Consistent with the results of these aforementioned studies, the findings of the current study revealed that miR-23b-3p expression was downregulated in CRC tissues.…”

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

“…MiR-217 encapsulated in exosomes exerts roles in promoting tumor cell proliferation, invasion, and EMT. 324 MiR-1246, a tumor inhibitor, was downregulated in PCa cell-derived exosomes. Overexpression of exosomal miR-1246 inhibits tumor cell proliferation, migration, and invasion and promoted cell apoptosis by suppressing EMT.…”

Exosomes: Isolation, characterization, and biomedical applications

“…Prostate antigen has been the most widely used biomarker, however exosomal miR-NAs have been recently proposed to distinguish aggressive from nonaggressive prostate cancers, guide treatment, and predict prognosis of disease (Lorenc et al, 2020). For instance, miR-217 and miR-23b-3p have been implicated in proliferation and invasion of prostate cancer, suggesting that they can be used as potential biomarkers and therapeutic targets in prostate cancer (C. Zhou et al, 2020).…”