DIFFERENTIAL EXPRESSION OF CIRCULAR RNAs IN THE FRONTAL CORTEX OF RATS UNDER ISCHEMIA-REPERFUSION CONDITIONS

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Abstract

Circular RNAs (circRNAs) are covalently closed non-coding RNAs that have increased metabolic stability and are capable of regulating gene expression. CircRNAs are considered as potential biomarkers and therapeutic targets for various diseases, including ischemic stroke. The transient right middle cerebral artery occlusion (tMCAO) model is actively used in stroke transcriptomics. In this study, we used whole-genome RNA sequencing to study the circRNA expression profile in the frontal cortex of rat brain 24 h after tMCAO. We identified 64 differentially expressed circRNAs (Fold change >1.5; Padj <0.05), which predominantly increased their levels compared to sham-operated animals. According to MRI data, the studied frontal cortex region included the penumbra zone, cell survival in which is important for stroke recovery. Also, using our previously obtained data on differential mRNA expression in this brain region, we bioinformatically predicted mRNA-miRNA-circRNA regulatory networks. Functional analysis of these networks showed that genes whose expression may depend on circRNA activity during ischemia are responsible for synaptic signaling and inflammatory response. Our study shows a significant role of circRNA-mediated transcriptome regulation in the penumbra-associated brain region during ischemia and allows us to consider circRNAs as potential targets for new strategies for the treatment of stroke and post-stroke complications.

About the authors

I. V. Mozgovoy

National Research Centre “Kurchatov Institute”

Moscow, Russia

Y. Y. Shpetko

National Research Centre “Kurchatov Institute”

Moscow, Russia

A. E. Denisova

Pirogov Russian National Research Medical University

Moscow, Russia

V. V. Stavchansky

National Research Centre “Kurchatov Institute”

Moscow, Russia

M. A. Vinogradina

National Research Centre “Kurchatov Institute”

Moscow, Russia

L. V. Gubsky

Pirogov Russian National Research Medical University; Federal Center for the Brain and Neurotechnology, Federal Medical Biological Agency

Moscow, Russia; Moscow, Russia

L. V. Dergunova

National Research Centre “Kurchatov Institute”

Moscow, Russia

S. A. Limborska

National Research Centre “Kurchatov Institute”

Moscow, Russia

I. B. Filippenkov

National Research Centre “Kurchatov Institute”

Email: filippenkov-ib.img@yandex.ru
Moscow, Russia

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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

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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».