Патофизиология микроРНК-146a при раке легких. Перспективы повышения эффективности таргетной терапии

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Аннотация

Рак легких — широко распространенная злокачественная опухоль дыхательных путей, наносит значительный урон здоровью человека. МикроРНК (miRNAs) являются небольшими, некодируемыми РНК размером примерно 20–25 нуклеотидов, которые функционируют как мощные модуляторы мРНК и белковых продуктов соответствующего гена. МикроРНК может смодулировать много биологических процессов, в том числе дифференцировку, пролиферацию, некроз и апоптоз клеток, и играет ключевую роль в патогенезе различных видов раковых новообразований. Накопившиеся данные последних лет доказали, что микроРНК, особенно микроРНК-146a, являются критическими модуляторами врожденных систем иммунного ответа. Новая и захватывающая область исследований рака включила микроРНК для обнаружения и супрессии рака. Однако фактический механизм, используемый этими микроРНК, все еще неясен. МикроРНК применялись в качестве связанного с раком биомаркера в ряде исследований, что предполагает их нарушенную экспрессию в различных видах рака по сравнению со здоровыми тканями. Уровень экспрессии микроРНК может также использоваться, чтобы определить стадию болезни, а также помочь при раннем обнаружении рака. Установлено, что при раке легких, панкреатическом и гепатоцеллюлярном раке, раке желудка, пролиферации раковых клеток и в метастазах уровень микроРНК-146а сильно подавлен. Изменения в уровнях экспрессии микроРНК служат хорошим биомаркером и обладают высоким прогностическим потенциалом для улучшения терапии при раке легких. Модуляция содержания микроРНК задерживает эпителиально-мезенхимальный переход и улучшает терапевтическое действие лекарственных средств. Полученные результаты позволяют предположить, что микроРНК-146a оказывает влияние на экспрессию гена через различные сигнальные пути: ФНО-α, NF-κB, MEK-1/2, JNK-1/2. Требуется дальнейшее исследование, чтобы понять детали молекулярных механизмов микроРНК-146a при раке легких, а также должна быть более подробно проанализирована роль микроРНК-146a в качестве диагностического маркера рака легких.

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Владимир Иванович Ващенко

Военно-медицинская академия им. С.М. Кирова

Автор, ответственный за переписку.
Email: vaschenko@yandex.ru

д-р биол. наук

Россия, 194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Юлия Евгеньевна Ромашова

Военно-медицинская академия им. С.М. Кирова

Email: vladimir-vaschenko@yandex.ru

зав. отделом Центра крови и тканей

Россия, 194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

Петр Дмитриевич Шабанов

Военно-медицинская академия им. С.М. Кирова

Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-код: 8974-7477

д-р мед. наук, профессор

Россия, 194044, Санкт-Петербург, ул. Академика Лебедева, д. 6

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