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

Abstract 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 RNA...

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Autores principales:	Weichen Wang, Longlong Wang, Mengyue Yang, Chunwei Wu, Rui Lan, Weiwei Wang, Yuze Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/6dfba9eb14e84524ac602a7cd1635ea5
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spelling	oai:doaj.org-article:6dfba9eb14e84524ac602a7cd1635ea52021-11-14T12:06:59ZCirc-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy10.1038/s41419-021-04059-y2041-4889https://doaj.org/article/6dfba9eb14e84524ac602a7cd1635ea52021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04059-yhttps://doaj.org/toc/2041-4889Abstract 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.Weichen WangLonglong WangMengyue YangChunwei WuRui LanWeiwei WangYuze LiNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Weichen Wang Longlong Wang Mengyue Yang Chunwei Wu Rui Lan Weiwei Wang Yuze Li Circ-SIRT1 inhibits cardiac hypertrophy via activating SIRT1 to promote autophagy
description	Abstract 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.
format	article
author	Weichen Wang Longlong Wang Mengyue Yang Chunwei Wu Rui Lan Weiwei Wang Yuze Li
author_facet	Weichen Wang Longlong Wang Mengyue Yang Chunwei Wu Rui Lan Weiwei Wang Yuze Li
author_sort	Weichen Wang
title	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_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_sort	circ-sirt1 inhibits cardiac hypertrophy via activating sirt1 to promote autophagy
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/6dfba9eb14e84524ac602a7cd1635ea5
work_keys_str_mv	AT weichenwang circsirt1inhibitscardiachypertrophyviaactivatingsirt1topromoteautophagy AT longlongwang circsirt1inhibitscardiachypertrophyviaactivatingsirt1topromoteautophagy AT mengyueyang circsirt1inhibitscardiachypertrophyviaactivatingsirt1topromoteautophagy AT chunweiwu circsirt1inhibitscardiachypertrophyviaactivatingsirt1topromoteautophagy AT ruilan circsirt1inhibitscardiachypertrophyviaactivatingsirt1topromoteautophagy AT weiweiwang circsirt1inhibitscardiachypertrophyviaactivatingsirt1topromoteautophagy AT yuzeli circsirt1inhibitscardiachypertrophyviaactivatingsirt1topromoteautophagy
_version_	1718429409158889472

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

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