The Role of Exosomal Circular RNA ZNF292 in Intermittent Hypoxia-induced AC16 Cardiomyocytes Injury

Overview

Journal Sleep Breath

Publisher Springer

Date 2023 Sep 19

PMID 37726500

Authors

Han-Sheng Xie

Jie-Feng Huang

Qiao-Xian Lin

Yue-Wen Chen

Gong-Ping Chen

Qi-Chang Lin

Affiliations

Soon will be listed here.

Abstract

Background: Exosomes are involved in cell-to-cell communication in numerous diseases including cardiovascular diseases, neurological diseases. Little attention has been dedicated to exosomal circular RNAs in obstructive sleep apnea (OSA)-related cardiovascular diseases. The aim of this study was to explore the role of exosomal circular RNA ZNF292 (circZNF292) on AC16 cells exposure to intermittent hypoxia (IH).

Methods: Exosome release inhibitor GW4869 was used to examine the effect of exosomes on IH-induced AC16 cells apoptosis. The expression of exosomal circZNF292 was detected by qRT-PCR in AC16 cells exposure to IH, and a luciferase reporter assay was conducted to confirm the connection between circZNF292 and miR-146a-5p. Exosomal circZNF292 was stably transfected with short hairpin RNAs (shRNAs) against circZNF292 and co-cultured with AC16 cells. The expression of miR-146a-5p and apoptosis-related protein was then measured to evaluate the effect of exosomal circZNF292.

Results: We found that IH contributed to the AC16 cells apoptosis, and the administration of GW4869 increased the apoptosis of cardiomyocytes when exposed to IH. The expression of exosomal circZNF292 decreased and miR-146a-5p increased significantly in AC16 cells exposed to IH compared to normoxic conditions. Bioinformatics analysis predicted a circZNF292/miR-146a-5p axis in IH-induced cardiomyocytes apoptosis. The dual-luciferase reporter system validated the direct interaction of circZNF292 and miR-146a-5p. Knockdown of circZNF292 increased the expressions of miR-146a-5p and accelerated the AC16 cardiomyocytes apoptosis.

Conclusions: The findings of this study suggested a novel mechanism by which exosomes transmit intrinsic regulatory signals to the myocardium through the exosomal circZNF292/miR-146a-5p axis. This finding highlights the potential of targeting this pathway as a therapeutic approach for treating cardiovascular diseases associated with OSA.

Citing Articles

Exosomes from IH- Induced bEnd3 Cells Promote OSA Cognitive Impairment via miR-20a-5p/MFN2 Mediated Pyroptosis of HT22 Cells.

Chen Z, Shang Y, Ou Y, Zhou L, Liu T, Gong S Nat Sci Sleep. 2024; 16:2063-2082.

PMID: 39717669 PMC: 11663995. DOI: 10.2147/NSS.S485952.

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