LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP Pathway

Long non-coding RNAs (lncRNAs) have been shown to play important roles in livestock fecundity, and many lncRNAs that affect follicular development and reproductive diseases have been identified in the ovary. However, only a few of them have been functionally annotated and mechanistically validated....

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Main Authors: Yong Wang, Yunxia Guo, Chunhui Duan, Junjie Li, Shoukun Ji, Huihui Yan, Yueqin Liu, Yingjie Zhang
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/20/12132
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author Yong Wang
Yunxia Guo
Chunhui Duan
Junjie Li
Shoukun Ji
Huihui Yan
Yueqin Liu
Yingjie Zhang
author_facet Yong Wang
Yunxia Guo
Chunhui Duan
Junjie Li
Shoukun Ji
Huihui Yan
Yueqin Liu
Yingjie Zhang
author_sort Yong Wang
collection DOAJ
description Long non-coding RNAs (lncRNAs) have been shown to play important roles in livestock fecundity, and many lncRNAs that affect follicular development and reproductive diseases have been identified in the ovary. However, only a few of them have been functionally annotated and mechanistically validated. In this study, we identified a new lncRNA (lncGSAR) and investigated its effects on the proliferation and steroidogenesis of ovine granulosa cells (GCs). High concentrations of glucose (add 33.6 mM glucose) caused high expression of lncGSAR in GCs by regulating its stability, and lncGSAR overexpression promoted GCs proliferation, estrogen secretion, and inhibited progesterone secretion, whereas interference with lncGASR had the opposite effect. Next, we found that the RNA molecules of lncGSAR act on MiR-125b as competitive endogenous RNA (ceRNA), and SREBP-cleavage-activating protein (SCAP) was verified as a target of MiR-125b. LncGASR overexpression increased the expression of SCAP, SREBP, and steroid hormone-related proteins, which can be attenuated by MiR-125b. Our results demonstrated that lncGSAR can act as a ceRNA to activate SCAP/SREBP signaling by sponging MiR-125b to regulate steroid hormone secretion in GCs. These findings provide new insights into the mechanisms of nutrient-regulated follicle development in ewes.
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spelling doaj.art-38ca71e7c32a414cab290298ac7fe8022023-12-02T00:31:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201213210.3390/ijms232012132LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP PathwayYong Wang0Yunxia Guo1Chunhui Duan2Junjie Li3Shoukun Ji4Huihui Yan5Yueqin Liu6Yingjie Zhang7Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaCollege of Life Science, Hebei Agricultural University, Baoding 071000, ChinaLaboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaLaboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaLaboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaLaboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaLaboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaLaboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaLong non-coding RNAs (lncRNAs) have been shown to play important roles in livestock fecundity, and many lncRNAs that affect follicular development and reproductive diseases have been identified in the ovary. However, only a few of them have been functionally annotated and mechanistically validated. In this study, we identified a new lncRNA (lncGSAR) and investigated its effects on the proliferation and steroidogenesis of ovine granulosa cells (GCs). High concentrations of glucose (add 33.6 mM glucose) caused high expression of lncGSAR in GCs by regulating its stability, and lncGSAR overexpression promoted GCs proliferation, estrogen secretion, and inhibited progesterone secretion, whereas interference with lncGASR had the opposite effect. Next, we found that the RNA molecules of lncGSAR act on MiR-125b as competitive endogenous RNA (ceRNA), and SREBP-cleavage-activating protein (SCAP) was verified as a target of MiR-125b. LncGASR overexpression increased the expression of SCAP, SREBP, and steroid hormone-related proteins, which can be attenuated by MiR-125b. Our results demonstrated that lncGSAR can act as a ceRNA to activate SCAP/SREBP signaling by sponging MiR-125b to regulate steroid hormone secretion in GCs. These findings provide new insights into the mechanisms of nutrient-regulated follicle development in ewes.https://www.mdpi.com/1422-0067/23/20/12132lncGSARMiR-125bceRNAgranulosa cellsteroidogenesis
spellingShingle Yong Wang
Yunxia Guo
Chunhui Duan
Junjie Li
Shoukun Ji
Huihui Yan
Yueqin Liu
Yingjie Zhang
LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP Pathway
International Journal of Molecular Sciences
lncGSAR
MiR-125b
ceRNA
granulosa cell
steroidogenesis
title LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP Pathway
title_full LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP Pathway
title_fullStr LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP Pathway
title_full_unstemmed LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP Pathway
title_short LncGSAR Controls Ovarian Granulosa Cell Steroidogenesis via Sponging MiR-125b to Activate SCAP/SREBP Pathway
title_sort lncgsar controls ovarian granulosa cell steroidogenesis via sponging mir 125b to activate scap srebp pathway
topic lncGSAR
MiR-125b
ceRNA
granulosa cell
steroidogenesis
url https://www.mdpi.com/1422-0067/23/20/12132
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