circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expression

Abstract Background Follicular atresia is a major determinant of ovarian failure in multiparous sows. Non-coding RNAs (ncRNAs) play an important role in the regulatory mechanisms controlling apoptosis within ovarian granulosa cells (GCs). Methods The circular structure of circVEGFA was validated by...

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Main Authors: Xinxin Qin, Jinbi Zhang, Chao Yin, Fan Li, Wenjie Li, Xiaolong Cheng, Xing Du, Qifa Li, Zengxiang Pan
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Ovarian Research
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Online Access:https://doi.org/10.1186/s13048-025-01738-8
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author Xinxin Qin
Jinbi Zhang
Chao Yin
Fan Li
Wenjie Li
Xiaolong Cheng
Xing Du
Qifa Li
Zengxiang Pan
author_facet Xinxin Qin
Jinbi Zhang
Chao Yin
Fan Li
Wenjie Li
Xiaolong Cheng
Xing Du
Qifa Li
Zengxiang Pan
author_sort Xinxin Qin
collection DOAJ
description Abstract Background Follicular atresia is a major determinant of ovarian failure in multiparous sows. Non-coding RNAs (ncRNAs) play an important role in the regulatory mechanisms controlling apoptosis within ovarian granulosa cells (GCs). Methods The circular structure of circVEGFA was validated by RNase R and actinomycin D treatments. The function of circVEGFA during apoptosis in GCs was investigated by si-RNA transfection. Furthermore, competitive binding of circVEGFA and TMX4 to miR-21-3p was confirmed by a dual-luciferase reporter gene assay and co-transfection with their inhibitors or siRNA. Results: In this study, we present a novel circular RNA (circRNA), circVEGFA, which shows significantly reduced expression in atretic follicles (AFs) compared to healthy follicles (HFs). Conclusions The study demonstrates that circVEGFA increases TMX4 expression and inhibits apoptosis in GCs through competitive binding to miR-21-3p. This study contributes to the understanding of circRNA regulation after follicular atresia.
format Article
id doaj-art-c38a6d0b08b9475db4a198d39d0b6c22
institution Kabale University
issn 1757-2215
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series Journal of Ovarian Research
spelling doaj-art-c38a6d0b08b9475db4a198d39d0b6c222025-08-20T03:46:16ZengBMCJournal of Ovarian Research1757-22152025-07-0118111310.1186/s13048-025-01738-8circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expressionXinxin Qin0Jinbi Zhang1Chao Yin2Fan Li3Wenjie Li4Xiaolong Cheng5Xing Du6Qifa Li7Zengxiang Pan8College of Animal Science and Technology, Nanjing Agriculture UniversityCollege of Animal Science and Food Engineering, Jinling Institute of TechnologyCollege of Animal Science and Food Engineering, Jinling Institute of TechnologyCollege of Animal Science and Food Engineering, Jinling Institute of TechnologyCollege of Animal Science and Technology, Nanjing Agriculture UniversityCollege of Animal Science and Technology, Nanjing Agriculture UniversityCollege of Animal Science and Technology, Nanjing Agriculture UniversityCollege of Animal Science and Technology, Nanjing Agriculture UniversityCollege of Animal Science and Technology, Nanjing Agriculture UniversityAbstract Background Follicular atresia is a major determinant of ovarian failure in multiparous sows. Non-coding RNAs (ncRNAs) play an important role in the regulatory mechanisms controlling apoptosis within ovarian granulosa cells (GCs). Methods The circular structure of circVEGFA was validated by RNase R and actinomycin D treatments. The function of circVEGFA during apoptosis in GCs was investigated by si-RNA transfection. Furthermore, competitive binding of circVEGFA and TMX4 to miR-21-3p was confirmed by a dual-luciferase reporter gene assay and co-transfection with their inhibitors or siRNA. Results: In this study, we present a novel circular RNA (circRNA), circVEGFA, which shows significantly reduced expression in atretic follicles (AFs) compared to healthy follicles (HFs). Conclusions The study demonstrates that circVEGFA increases TMX4 expression and inhibits apoptosis in GCs through competitive binding to miR-21-3p. This study contributes to the understanding of circRNA regulation after follicular atresia.https://doi.org/10.1186/s13048-025-01738-8Follicular atresiaGranulosa cell apoptosiscircRNAmiRNATMX4
spellingShingle Xinxin Qin
Jinbi Zhang
Chao Yin
Fan Li
Wenjie Li
Xiaolong Cheng
Xing Du
Qifa Li
Zengxiang Pan
circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expression
Journal of Ovarian Research
Follicular atresia
Granulosa cell apoptosis
circRNA
miRNA
TMX4
title circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expression
title_full circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expression
title_fullStr circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expression
title_full_unstemmed circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expression
title_short circVEGFA inhibits apoptosis in porcine ovarian granulosa cells by binding to miR-21-3p and up-regulating TMX4 expression
title_sort circvegfa inhibits apoptosis in porcine ovarian granulosa cells by binding to mir 21 3p and up regulating tmx4 expression
topic Follicular atresia
Granulosa cell apoptosis
circRNA
miRNA
TMX4
url https://doi.org/10.1186/s13048-025-01738-8
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AT chaoyin circvegfainhibitsapoptosisinporcineovariangranulosacellsbybindingtomir213pandupregulatingtmx4expression
AT fanli circvegfainhibitsapoptosisinporcineovariangranulosacellsbybindingtomir213pandupregulatingtmx4expression
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AT xingdu circvegfainhibitsapoptosisinporcineovariangranulosacellsbybindingtomir213pandupregulatingtmx4expression
AT qifali circvegfainhibitsapoptosisinporcineovariangranulosacellsbybindingtomir213pandupregulatingtmx4expression
AT zengxiangpan circvegfainhibitsapoptosisinporcineovariangranulosacellsbybindingtomir213pandupregulatingtmx4expression