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Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy

Mounting studies have substantiated that abrogating autophagy contributes to cardiac hypertrophy (CH). Sirtuin 1 (SIRT1) has been reported to support autophagy and inhibit CH. However, the upstream regulation mechanism behind the regulation of SIRT1 level in CH remains unclear. Circular RNAs (circRN...

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Autores principales: Wang, Weichen, Wang, Longlong, Yang, Mengyue, Wu, Chunwei, Lan, Rui, Wang, Weiwei, Li, Yuze
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580993/
https://www.ncbi.nlm.nih.gov/pubmed/34759275
http://dx.doi.org/10.1038/s41419-021-04059-y
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author Wang, Weichen
Wang, Longlong
Yang, Mengyue
Wu, Chunwei
Lan, Rui
Wang, Weiwei
Li, Yuze
author_facet Wang, Weichen
Wang, Longlong
Yang, Mengyue
Wu, Chunwei
Lan, Rui
Wang, Weiwei
Li, Yuze
author_sort Wang, Weichen
collection PubMed
description Mounting studies have substantiated that abrogating autophagy contributes to cardiac hypertrophy (CH). Sirtuin 1 (SIRT1) has been reported to support autophagy and inhibit CH. However, the upstream regulation mechanism behind the regulation of SIRT1 level in CH remains unclear. Circular RNAs (circRNAs) are vital modulators in diverse human diseases including CH. This study intended to investigate the regulatory mechanism of circRNA on SIRT1 expression in CH. CH model was established by angiotensin II (Ang II) fusion or transverse aortic constriction (TAC) surgery and Ang II treatment on hiPSC-CMs and H9c2 cells in vitro. Our results showed that circ-SIRT1 (hsa_circ_0093884) expression was downregulated in Ang II-treated hiPSC-CMs, and confirmed that its conserved mouse homolog circ-Sirt1 (mmu_circ_0002354) was expressed at low levels in Ang II-treated H9c2 cells and TAC-induced mice model. Functionally, circ-SIRT1/circ-Sirt1 attenuated Ang II-induced CH and induced autophagy in hiPSC-CMs and H9c2 cardiomyocytes. Mechanistically, circ-SIRT1 could upregulate its host gene SIRT1 at the post-transcriptional level by sponging miR-3681-3p/miR-5195-3p and stabilized SIRT1 protein at the post-translational level by recruiting USP22 to induce deubiquitination on SIRT1 protein. Further, SIRT1 knockdown could rescue the effect of circ-SIRT1 upregulation on Ang II-induced CH and autophagy in vitro and in vivo. In conclusion, we first uncovered that circ-SIRT1 restrains CH via activating SIRT1 to promote autophagy, indicating circ-SIRT1 as a promising target to alleviate CH.
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spelling pubmed-85809932021-11-15 Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy Wang, Weichen Wang, Longlong Yang, Mengyue Wu, Chunwei Lan, Rui Wang, Weiwei Li, Yuze Cell Death Dis Article Mounting studies have substantiated that abrogating autophagy contributes to cardiac hypertrophy (CH). Sirtuin 1 (SIRT1) has been reported to support autophagy and inhibit CH. However, the upstream regulation mechanism behind the regulation of SIRT1 level in CH remains unclear. Circular RNAs (circRNAs) are vital modulators in diverse human diseases including CH. This study intended to investigate the regulatory mechanism of circRNA on SIRT1 expression in CH. CH model was established by angiotensin II (Ang II) fusion or transverse aortic constriction (TAC) surgery and Ang II treatment on hiPSC-CMs and H9c2 cells in vitro. Our results showed that circ-SIRT1 (hsa_circ_0093884) expression was downregulated in Ang II-treated hiPSC-CMs, and confirmed that its conserved mouse homolog circ-Sirt1 (mmu_circ_0002354) was expressed at low levels in Ang II-treated H9c2 cells and TAC-induced mice model. Functionally, circ-SIRT1/circ-Sirt1 attenuated Ang II-induced CH and induced autophagy in hiPSC-CMs and H9c2 cardiomyocytes. Mechanistically, circ-SIRT1 could upregulate its host gene SIRT1 at the post-transcriptional level by sponging miR-3681-3p/miR-5195-3p and stabilized SIRT1 protein at the post-translational level by recruiting USP22 to induce deubiquitination on SIRT1 protein. Further, SIRT1 knockdown could rescue the effect of circ-SIRT1 upregulation on Ang II-induced CH and autophagy in vitro and in vivo. In conclusion, we first uncovered that circ-SIRT1 restrains CH via activating SIRT1 to promote autophagy, indicating circ-SIRT1 as a promising target to alleviate CH. Nature Publishing Group UK 2021-11-10 /pmc/articles/PMC8580993/ /pubmed/34759275 http://dx.doi.org/10.1038/s41419-021-04059-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Weichen
Wang, Longlong
Yang, Mengyue
Wu, Chunwei
Lan, Rui
Wang, Weiwei
Li, Yuze
Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy
title Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy
title_full Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy
title_fullStr Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy
title_full_unstemmed Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy
title_short Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy
title_sort circ-sirt1 inhibits cardiac hypertrophy via activating sirt1 to promote autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580993/
https://www.ncbi.nlm.nih.gov/pubmed/34759275
http://dx.doi.org/10.1038/s41419-021-04059-y
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