MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that poses a great threat to women's health. MiR-1224-5p is downregulated in the follicular fluid of patients with PCOS, but its role remains largely unknown. In this study, mice were treated with dehydroepiandrosterone (DHEA) to e...

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Autores principales:	Yan Li, Nianling Yao, Yan Gao, Yunping Wang, Lu Bai, Jia Xu, Haixu Wang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	polycystic ovary syndrome mir-1224-5p human ovarian granulosa cells nlrp3 inflammasome foxo1 Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/4647694deb114d3db1bd8dd500dea72e
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spelling	oai:doaj.org-article:4647694deb114d3db1bd8dd500dea72e2021-11-17T14:21:59ZMiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 12165-59792165-598710.1080/21655979.2021.1987125https://doaj.org/article/4647694deb114d3db1bd8dd500dea72e2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1987125https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Polycystic ovary syndrome (PCOS) is a common endocrine disorder that poses a great threat to women's health. MiR-1224-5p is downregulated in the follicular fluid of patients with PCOS, but its role remains largely unknown. In this study, mice were treated with dehydroepiandrosterone (DHEA) to establish an in vivo model of PCOS. We found that enhanced activation of NLRP3 inflammasome was accompanied by downregulation of miR-1224-5p in ovarian tissue of PCOS mice. The effect of miR-1224-5p was further explored in TNF-α-treated human granulosa-like tumor (KGN) cells. Upregulation of miR-1224-5p suppressed TNF-α-induced secretion of DHEA and testosterone. MiR-1224-5p attenuated TNF-α-induced inflammation by inhibiting NLRP3 inflammasome activation, IL-1β synthesis, and nuclear factor kappa B (NF-κB) p65 nuclear translocation. Notably, miR-1224-5p decreased the expression of Forkhead box O 1 (FOXO1) and its downstream gene thioredoxin interaction protein (TXNIP). Luciferase reporter assay confirmed FOXO1 as a target of miR-1224-5p. Upregulation of FOXO1 abolished miR-1224-5p-induced activation of NLRP3 inflammasome, demonstrating that miR-1224-5p might inhibit NLRP3 inflammasome activation through regulating FOXO1. This study provided novel insights into the pathogenesis of PCOS and suggested that miR-1224-5p might be a promising target for treating PCOS.Yan LiNianling YaoYan GaoYunping WangLu BaiJia XuHaixu WangTaylor & Francis Grouparticlepolycystic ovary syndromemir-1224-5phuman ovarian granulosa cellsnlrp3 inflammasomefoxo1BiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 1, Pp 8555-8569 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	polycystic ovary syndrome mir-1224-5p human ovarian granulosa cells nlrp3 inflammasome foxo1 Biotechnology TP248.13-248.65
spellingShingle	polycystic ovary syndrome mir-1224-5p human ovarian granulosa cells nlrp3 inflammasome foxo1 Biotechnology TP248.13-248.65 Yan Li Nianling Yao Yan Gao Yunping Wang Lu Bai Jia Xu Haixu Wang MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1
description	Polycystic ovary syndrome (PCOS) is a common endocrine disorder that poses a great threat to women's health. MiR-1224-5p is downregulated in the follicular fluid of patients with PCOS, but its role remains largely unknown. In this study, mice were treated with dehydroepiandrosterone (DHEA) to establish an in vivo model of PCOS. We found that enhanced activation of NLRP3 inflammasome was accompanied by downregulation of miR-1224-5p in ovarian tissue of PCOS mice. The effect of miR-1224-5p was further explored in TNF-α-treated human granulosa-like tumor (KGN) cells. Upregulation of miR-1224-5p suppressed TNF-α-induced secretion of DHEA and testosterone. MiR-1224-5p attenuated TNF-α-induced inflammation by inhibiting NLRP3 inflammasome activation, IL-1β synthesis, and nuclear factor kappa B (NF-κB) p65 nuclear translocation. Notably, miR-1224-5p decreased the expression of Forkhead box O 1 (FOXO1) and its downstream gene thioredoxin interaction protein (TXNIP). Luciferase reporter assay confirmed FOXO1 as a target of miR-1224-5p. Upregulation of FOXO1 abolished miR-1224-5p-induced activation of NLRP3 inflammasome, demonstrating that miR-1224-5p might inhibit NLRP3 inflammasome activation through regulating FOXO1. This study provided novel insights into the pathogenesis of PCOS and suggested that miR-1224-5p might be a promising target for treating PCOS.
format	article
author	Yan Li Nianling Yao Yan Gao Yunping Wang Lu Bai Jia Xu Haixu Wang
author_facet	Yan Li Nianling Yao Yan Gao Yunping Wang Lu Bai Jia Xu Haixu Wang
author_sort	Yan Li
title	MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1
title_short	MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1
title_full	MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1
title_fullStr	MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1
title_full_unstemmed	MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1
title_sort	mir-1224-5p attenuates polycystic ovary syndrome through inhibiting nod-like receptor protein 3 inflammasome activation via targeting forkhead box o 1
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/4647694deb114d3db1bd8dd500dea72e
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_version_	1718425412204232704

MiR-1224-5p attenuates polycystic ovary syndrome through inhibiting NOD-like receptor protein 3 inflammasome activation via targeting Forkhead box O 1

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