Circular RNAs in eukaryotic cells: origin, characteristics, mechanisms of molecular functioning in human malignant diseases

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Abstract

Circular RNAs (circRNAs) are an evolutionarily conserved novel class of non-coding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome, originally believed to be aberrant RNA splicing by-products with limited functionality.

However, recent advances in highthroughput genomic technology have allowed circRNAs to be characterized in detail and revealed their important functions in controlling various biological and molecular processes, the most essential being gene regulation. Due to structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA 2 biology. Unlike linear RNAs, circRNAs are produced differentially by backsplicing exons or “lariat” introns from a pre-messenger RNA (mRNA) forming covalently closed loop-like molecules missing 3' poly-(A) tail or 5' cap structures, thus rendering them resistant to exonuclease-mediated degradation.

Previous studies have revealed multiple roles of circRNAs as “sponges” for miRNA and RNA-binding proteins (RBP), as well as regulators of transcription, translation, and splicing events. Recent advances in the field suggest that the circRNAs are involved in many human disorders, including cancer and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, due to their aberrant expression in different pathological conditions. The circRNAs are stable in cells, owing to their circular structure. Participation of circRNAs in programmed cellular destruction by autophagy is discussed in details. The autophagy is a catabolic process which promotes decomposition and recycling of harmful or redundant biological macromolecules and initiates destruction of ageing cells. Processes how circRNAs influence a course of a disease, including an autophagy are in detail discussed, specifying that it joins at the beginning and upon development of various illnesses, and it can influence drug resistance (for example, antitumor efficiency of Cisplatin).

The functional versatility exhibited by circRNAs enables them to serve as potential diagnostic or predictive biomarkers for various diseases. This review discusses the properties, characterization, profiling, and the diverse molecular actions of circRNAs and their usage as potential therapeutic targets in different human malignancies.

About the authors

Vladimir I. Vashchenko

Kirov Military Medical Academy

Author for correspondence.
Email: vladimir-vaschenko@yandex.ru

Dr. Sci. (Biol)., Head of the Department of Biochemistry, Centre of Blood and Tissues

Russian Federation, Saint Petersburg

Alexey B. Chuklovin

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantology, Academician I.P. Pavlov First St. Petersburg State Medical University

Email: alexei.chukh@mail.ru
SPIN-code: 3050-7030

MD, Dr. Sci. (Med.), Professor, Head of the Laboratory of Transplantology

Russian Federation, Saint Petersburg

Petr D. Shabanov

Kirov Military Medical Academy

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

Dr. Sci. (Med.), Professor, Professor of the Department of Pharmacology

Russian Federation, Saint Petersburg

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Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».