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Article

A New Approach for Prostate Cancer Diagnosis by miRNA Profiling of Prostate-Derived Plasma Small Extracellular Vesicles

1
Department of Radiotherapy, Subcellular Technology Laboratory, N.N. Petrov National Medical Research Center of Oncology, 197758 St. Petersburg, Russia
2
Oncosystem Ltd., 121205 Moscow, Russia
3
Department of Andrology and Urology, Research Center of Urology, Pavlov First Saint Petersburg State Medical University, 197022 St. Petersburg, Russia
*
Authors to whom correspondence should be addressed.
Academic Editors: Fabrizio Fontana, Maria Felice Brizzi and Priya Samuel
Cells 2021, 10(9), 2372; https://doi.org/10.3390/cells10092372
Received: 27 July 2021 / Revised: 5 September 2021 / Accepted: 7 September 2021 / Published: 9 September 2021
Vesicular miRNA has emerged as a promising marker for various types of cancer, including prostate cancer (PC). In the advanced stage of PC, the cancer-cell-derived small extracellular vesicles (SEVs) may constitute a significant portion of circulating vesicles and may mediate a detectable change in the plasma vesicular miRNA profile. However, SEVs secreted by small tumor in the prostate gland constitute a tiny fraction of circulating vesicles and cause undetectable miRNA pattern changes. Thus, the isolation and miRNA profiling of a specific prostate-derived fraction of SEVs can improve the diagnostic potency of the methods based on vesicular miRNA analysis. Prostate-specific membrane antigen (PSMA) was selected as a marker of prostate-derived SEVs. Super-paramagnetic beads (SPMBs) were functionalized by PSMA-binding DNA aptamer (PSMA–Apt) via a click reaction. The efficacy of SPMB–PSMA–Apt complex formation and PSMA(+)SEVs capture were assayed by flow cytometry. miRNA was isolated from the total population of SEVs and PSMA(+)SEVs of PC patients (n = 55) and healthy donors (n = 30). Four PC-related miRNAs (miR-145, miR-451a, miR-143, and miR-221) were assayed by RT-PCR. The click chemistry allowed fixing DNA aptamers onto the surface of SPMB with an efficacy of up to 89.9%. The developed method more effectively isolates PSMA(+)SEVs than relevant antibody-based technology. The analysis of PC-related miRNA in the fraction of PSMA(+)SEVs was more sensitive and revealed distinct diagnostic potency (AUC: miR-145, 0.76; miR-221, 0.7; miR-451a, 0.65; and miR-141, 0.64) than analysis of the total SEV population. Thus, isolation of prostate-specific SEVs followed by analysis of vesicular miRNA might be a promising PC diagnosis method. View Full-Text
Keywords: prostate cancer; diagnostics; small extracellular vesicles; SEVs; microRNA; miRNA; PSMA; PSMA(+)SEVs; click chemistry prostate cancer; diagnostics; small extracellular vesicles; SEVs; microRNA; miRNA; PSMA; PSMA(+)SEVs; click chemistry
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MDPI and ACS Style

Zabegina, L.; Nazarova, I.; Nikiforova, N.; Slyusarenko, M.; Sidina, E.; Knyazeva, M.; Tsyrlina, E.; Novikov, S.; Reva, S.; Malek, A. A New Approach for Prostate Cancer Diagnosis by miRNA Profiling of Prostate-Derived Plasma Small Extracellular Vesicles. Cells 2021, 10, 2372. https://doi.org/10.3390/cells10092372

AMA Style

Zabegina L, Nazarova I, Nikiforova N, Slyusarenko M, Sidina E, Knyazeva M, Tsyrlina E, Novikov S, Reva S, Malek A. A New Approach for Prostate Cancer Diagnosis by miRNA Profiling of Prostate-Derived Plasma Small Extracellular Vesicles. Cells. 2021; 10(9):2372. https://doi.org/10.3390/cells10092372

Chicago/Turabian Style

Zabegina, Lidia, Inga Nazarova, Nadezhda Nikiforova, Maria Slyusarenko, Elena Sidina, Margarita Knyazeva, Evgenia Tsyrlina, Sergey Novikov, Sergey Reva, and Anastasia Malek. 2021. "A New Approach for Prostate Cancer Diagnosis by miRNA Profiling of Prostate-Derived Plasma Small Extracellular Vesicles" Cells 10, no. 9: 2372. https://doi.org/10.3390/cells10092372

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