lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1

The list of long non-coding RNAs (lncRNAs) that participate in the function of ovarian granulosa cells (GCs) is rapidly expanding, but the mechanisms through which lncRNAs regulate GC function are not yet fully understood. Here, we recognized a minimally expressed lncRNA RP4-545C24.1 (which we named...

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Autores principales:	Duan Li, Weiwei Xu, Xiaoyan Wang, Yujie Dang, Lan Xu, Gang Lu, Wai-Yee Chan, Peter C.K. Leung, Shidou Zhao, Yingying Qin
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	premature ovarian insufficiency granulosa cells lncRNA WT1 RAD51 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5ad116309fca4af59cca967b3f6b123c
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spelling	oai:doaj.org-article:5ad116309fca4af59cca967b3f6b123c2021-11-04T04:28:40ZlncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT12162-253110.1016/j.omtn.2021.10.015https://doaj.org/article/5ad116309fca4af59cca967b3f6b123c2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2162253121002584https://doaj.org/toc/2162-2531The list of long non-coding RNAs (lncRNAs) that participate in the function of ovarian granulosa cells (GCs) is rapidly expanding, but the mechanisms through which lncRNAs regulate GC function are not yet fully understood. Here, we recognized a minimally expressed lncRNA RP4-545C24.1 (which we named DDGC) in GCs from patients with biochemical premature ovarian insufficiency (bPOI). We further explored the role of lncRNA DDGC in GC function and its contribution to the development of bPOI. Mechanistically, silencing DDGC downregulated RAD51 by competitively binding with miR-589-5p, and this resulted in significant inhibition of DNA damage repair capacity. In addition, decreased expression of DDGC promoted ubiquitin-mediated degradation of Wilms tumor 1 (WT1) protein through interactions with heat shock protein 90 (HSP90), which led to aberrant differentiation of GCs. Moreover, DDGC was able to ameliorate the etoposide-induced DNA damage and apoptosis in vivo. Taken together, these findings provide new insights into the contribution of lncRNAs in POI pathogenesis.Duan LiWeiwei XuXiaoyan WangYujie DangLan XuGang LuWai-Yee ChanPeter C.K. LeungShidou ZhaoYingying QinElsevierarticlepremature ovarian insufficiencygranulosa cellslncRNAWT1RAD51Therapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1092-1106 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	premature ovarian insufficiency granulosa cells lncRNA WT1 RAD51 Therapeutics. Pharmacology RM1-950
spellingShingle	premature ovarian insufficiency granulosa cells lncRNA WT1 RAD51 Therapeutics. Pharmacology RM1-950 Duan Li Weiwei Xu Xiaoyan Wang Yujie Dang Lan Xu Gang Lu Wai-Yee Chan Peter C.K. Leung Shidou Zhao Yingying Qin lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1
description	The list of long non-coding RNAs (lncRNAs) that participate in the function of ovarian granulosa cells (GCs) is rapidly expanding, but the mechanisms through which lncRNAs regulate GC function are not yet fully understood. Here, we recognized a minimally expressed lncRNA RP4-545C24.1 (which we named DDGC) in GCs from patients with biochemical premature ovarian insufficiency (bPOI). We further explored the role of lncRNA DDGC in GC function and its contribution to the development of bPOI. Mechanistically, silencing DDGC downregulated RAD51 by competitively binding with miR-589-5p, and this resulted in significant inhibition of DNA damage repair capacity. In addition, decreased expression of DDGC promoted ubiquitin-mediated degradation of Wilms tumor 1 (WT1) protein through interactions with heat shock protein 90 (HSP90), which led to aberrant differentiation of GCs. Moreover, DDGC was able to ameliorate the etoposide-induced DNA damage and apoptosis in vivo. Taken together, these findings provide new insights into the contribution of lncRNAs in POI pathogenesis.
format	article
author	Duan Li Weiwei Xu Xiaoyan Wang Yujie Dang Lan Xu Gang Lu Wai-Yee Chan Peter C.K. Leung Shidou Zhao Yingying Qin
author_facet	Duan Li Weiwei Xu Xiaoyan Wang Yujie Dang Lan Xu Gang Lu Wai-Yee Chan Peter C.K. Leung Shidou Zhao Yingying Qin
author_sort	Duan Li
title	lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1
title_short	lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1
title_full	lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1
title_fullStr	lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1
title_full_unstemmed	lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1
title_sort	lncrna ddgc participates in premature ovarian insufficiency through regulating rad51 and wt1
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5ad116309fca4af59cca967b3f6b123c
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lncRNA DDGC participates in premature ovarian insufficiency through regulating RAD51 and WT1

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