LncRNA FAF attenuates hypoxia/ischaemia‐induced pyroptosis via the miR‐185‐5p/PAK2 axis in cardiomyocytes

Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore...

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Published in:Journal of cellular and molecular medicine Vol. 26; no. 10; pp. 2895 - 2907
Main Authors: Gu, Jie, Shi, Jian‐Zhou, Wang, Ya‐Xing, Liu, Liu, Wang, Si‐Bo, Sun, Jia‐Teng, Shan, Tian‐Kai, Wang, Hao, Wang, Qi‐Ming, Wang, Lian‐Sheng
Format: Journal Article
Language:English
Published: England John Wiley & Sons, Inc 01.05.2022
John Wiley and Sons Inc
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ISSN:1582-1838, 1582-4934, 1582-4934
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Summary:Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore the antipyroptotic effects of lncRNA FGF9‐associated factor (FAF) in acute myocardial infarction (AMI). The expression patterns of lncRNA FAF, miR‐185‐5p and P21 activated kinase 2 (PAK2) were detected in hypoxia/ischaemia‐induced cardiomyocytes. Hoechst 33342/PI staining, lactate dehydrogenase (LDH) release assay, immunofluorescence and Western blotting were conducted to assay cell pyroptosis. The interaction between lncRNA FAF, miR‐185‐5p and PAK2 was verified by bioinformatics analysis, small RNA sequencing luciferase reporter assay and qRT‐PCR. The expression of LncRNA FAF was downregulated in hypoxic cardiomyocytes and myocardial tissues. Overexpression of lncRNA FAF could attenuate cardiomyocyte pyroptosis, improve cell viability and reduce infarct size during the procession of AMI. Moreover, lncRNA FAF was confirmed as a sponge of miR‐185‐5p and promoted PAK2 expression in cardiomyocytes. Collectively, our findings reveal a novel lncRNA FAF/miR‐185‐5p/PAK2 axis as a crucial regulator in cardiomyocyte pyroptosis, which might be a potential therapeutic target of AMI.
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Jie Gu and Jian‐Zhou Shi contributed equally to this work.
ISSN:1582-1838
1582-4934
1582-4934
DOI:10.1111/jcmm.17304