Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press64910.17650/2313-805X-2024-11-1-55-78EXPERIMENTAL REPORTЭКСПЕРИМЕНТАЛЬНАЯ СТАТЬЯUnknownDynamics of miRNA expression in urine extracellular vesicles of prostate cancer patients after radical prostatectomyДинамика экспрессии микроРНК внеклеточных везикул мочи больных раком предстательной железы после радикальной простатэктомииhttps://orcid.org/0009-0004-3004-8969ShutkoE. V.ШуткоЕ. В.
Russian Federation

Ekaterina Viktorovna Shutko

8 Academician Lavrentiev Prospekt, Novosibirsk 630090; 1 Pirogov St., Novosibirsk 630090

Екатерина Викторовна Шутко

630090 Новосибирск, проспект Академика Лаврентьева, 8; 630090 Новосибирск, ул. Пирогова, 1

katshutko@gmail.comhttps://orcid.org/0000-0003-3433-7261BryzgunovaO. E.БрызгуноваО. Е.
Russian Federation

8 Academician Lavrentiev Prospekt, Novosibirsk 630090

630090 Новосибирск, проспект Академика Лаврентьева, 8

info@abvpress.ruOstal’cevI. A.ОстальцевИ. А.
Russian Federation

15 Rechkunovskaya St., Novosibirsk 630055

630055 Новосибирск, ул. Речкуновская, 15

info@abvpress.ruhttps://orcid.org/0009-0009-6221-2758PakS. V.ПакС. В.
Russian Federation

15 Rechkunovskaya St., Novosibirsk 630055

630055 Новосибирск, ул. Речкуновская, 15

info@abvpress.ruKrasi’nikovS. E.КрасильниковС. Э.
Russian Federation

15 Rechkunovskaya St., Novosibirsk 630055

630055 Новосибирск, ул. Речкуновская, 15

info@abvpress.ruLaktionovP. P.ЛактионовП. П.
Russian Federation

8 Academician Lavrentiev Prospekt, Novosibirsk 630090; 15 Rechkunovskaya St., Novosibirsk 630055

630090 Новосибирск, проспект Академика Лаврентьева, 8; 630055 Новосибирск, ул. Речкуновская, 15

info@abvpress.ruhttps://orcid.org/0000-0003-2925-9350KonoshenkoM. Yu.КоношенкоМ. Ю.
Russian Federation

8 Academician Lavrentiev Prospekt, Novosibirsk 630090

630090 Новосибирск, проспект Академика Лаврентьева, 8

info@abvpress.ruInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of SciencesФГБУН «Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук»Novosibirsk State UniversityФГАОУ ВО «Новосибирский национальный исследовательский государственный университет»E.N. Meshalkin National Medical Research Center, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр им. акад. Е.Н. Мешалкина» Минздрава России1501202411155780504202405042024Copyright ©; 2024, Shutko E.V., Bryzgunova O.E., Ostal’cev I.A., Pak S.V., Krasi’nikov S.E., Laktionov P.P., Konoshenko M.Y.Copyright ©; 2024, Шутко Е.В., Брызгунова О.Е., Остальцев И.А., Пак С.В., Красильников С.Э., Лактионов П.П., Коношенко М.Ю.2024Shutko E.V., Bryzgunova O.E., Ostal’cev I.A., Pak S.V., Krasi’nikov S.E., Laktionov P.P., Konoshenko M.Y.Шутко Е.В., Брызгунова О.Е., Остальцев И.А., Пак С.В., Красильников С.Э., Лактионов П.П., Коношенко М.Ю.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/649

Introduction. It is known that the treatment of oncological diseases including prostate cancer (PCa) causes changes in the expression of oncogenic and oncosuppressive miRNAs. The analysis of miRNA expression dynamics can be used to predict the course of the disease and its response to therapy. However, the effect of PCa therapy on the expression of extracellular miRNAs is just beginning to be investigated.

Aim. To study the expression dynamics of 14 miRNAs (miR-19b, -22-3p, -30e, -31, -92a, -125b, -144, -200b, -205, -222, -375, -378a, -425, -660) in urine extracellular vesicles of PCa patients after radical prostatectomy and to reveal prognostic miRNA ratios.

Materials and methods. Urine samples of 18 donors and 18 PCa patients, obtained before radical prostatectomy, 1 week and 3 months after surgery, were examined. Extracellular vesicles were isolated by aggregation-precipitation protocol; extracellular vesicles miRNAs were isolated using fiberglass sorbents and octane acid. Data on threshold detection cycles of 14 miRNAs were obtained using reverse transcription – loop polymerase chain reaction (TaqMan).

Results. It was found that prostatectomy causes a significant change in the relative expression of 44 miRNA ratios in the urine of PCa patients. Four groups of miRNA ratios can be distinguished: 1) miRNA ratios, which expression level significantly differed between donors and PCa patients before surgery and significantly changed in PCa patients 3 months after prostatectomy in the direction of the level of donors (6 pairs); 2) miRNA ratios, which expression did not significantly differ between donors and PCa patients before surgery, but significantly differed from the baseline in PCa patients and donors 3 months after prostatectomy (5 pairs); 3) miRNA ratios, based on expression ratios of which PCa patients can be divided into two or three significantly different subgroups 3 months after prostatectomy (19 pairs); 4) miRNA ratios that did not significantly change their expression after prostatectomy (30 pairs).

Conclusion. Prostatectomy causes a significant change in the level of expression of miRNA in urine. 6 pairs of miRNAs, the relative expression of which after surgery significantly changed towards that of healthy donors and 19 pairs of miRNAs, according to the level of relative expression of which patients with prostate cancer were divided into two significantly different subgroups 3 months after prostatectomy, were identified based on the analysis of the dynamics of miRNA expression after prostatectomy.

Введение. Известно, что лечение онкологических заболеваний, в том числе рака предстательной железы (РПЖ), вызывает изменения экспрессии онкогенных и онкосупрессорных микроРНК. Анализ динамики их экспрессии может быть использован для прогнозирования течения заболевания и ответа на терапию. Тем не менее влияние лечения РПЖ на экспрессию внеклеточных микроРНК только начинает исследоваться.

Цель исследования – изучить динамику экспрессии 14 микроРНК (miR-19b, -22-3p, -30e, -31, -92a, -125b, -144, -200b, -205, -222, -375, -378a, -425, -660) внеклеточных везикул мочи больных РПЖ после радикальной простатэктомии и выявить прогностические пары микроРНК.

Материалы и методы. Исследованы образцы мочи 18 доноров и 18 больных РПЖ, полученные до радикальной простатэктомии, через 1 нед и спустя 3 мес после операции. Внеклеточные везикулы выделены методом агрегации– преципитации, их микроРНК – с использованием стекловолокнистых сорбентов и октановой кислоты. С помощью обратной транскрипции – петлевой полимеразной цепной реакции (TaqMan) – получены данные о пороговых циклах детекции 14 микроРНК.

Результаты. Обнаружено, что радикальная простатэктомия вызывает достоверное изменение относительной экспрессии 44 пар микроРНК во внеклеточных везикулах мочи больных РПЖ. Можно выделить 4 группы пар микроРНК: 1) пары микроРНК, уровень экспрессии которых достоверно различался между донорами и больными РПЖ до операции и достоверно изменялся у больных РПЖ через 3 мес после нее по направлению к уровню доноров (6 пар); 2) пары микроРНК, уровень экспрессии которых достоверно не различался между донорами и больными РПЖ до операции, однако через 3 мес после нее достоверно отличался от исходного у больных РПЖ и доноров (5 пар); 3) пары микроРНК, на основании данных об относительной экспрессии которых больных РПЖ через 3 мес после радикальной простатэктомии можно разделить на 2 или 3 достоверно различающиеся подгруппы (19 пар); 4) пары микроРНК, достоверно не изменившие свою экспрессию после операции (30 пар).

Заключение. Радикальная простатэктомия вызывает значительное изменение уровня экспрессии микроРНК внеклеточных везикул мочи. На основании анализа динамики экспрессии микроРНК после этой операции выявлены 6 пар микроРНК, уровень относительной экспрессии которых после хирургического вмешательства достоверно изменялся в сторону ее уровня у здоровых доноров, и 19 пар микроРНК, по уровню относительной экспрессии которых больные РПЖ разделялись на 2 достоверно различные подгруппы через 3 мес после радикальной простатэктомии.

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