NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis
Abstract Background Follicular atresia has been shown to be strongly associated with a low follicle utilization rate and female infertility, which are regulated by many factors such as microRNAs (miRNAs), which constitute a class of noncoding RNAs (ncRNAs). However, little is known about long noncod...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Journal of Animal Science and Biotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40104-021-00626-7 |
| _version_ | 1818719145977446400 |
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| author | Wang Yao Zengxiang Pan Xing Du Jinbi Zhang Honglin Liu Qifa Li |
| author_facet | Wang Yao Zengxiang Pan Xing Du Jinbi Zhang Honglin Liu Qifa Li |
| author_sort | Wang Yao |
| collection | DOAJ |
| description | Abstract Background Follicular atresia has been shown to be strongly associated with a low follicle utilization rate and female infertility, which are regulated by many factors such as microRNAs (miRNAs), which constitute a class of noncoding RNAs (ncRNAs). However, little is known about long noncoding RNAs (lncRNAs), which constitute another ncRNA family that regulate follicular atresia. Results A total of 77 differentially expressed lncRNAs, including 67 upregulated and 10 downregulated lncRNAs, were identified in early atretic follicles compared to healthy follicles by RNA-Sequencing. We characterized a noncoding RNA that was highly expressed in atretic follicles (NORHA). As an intergenic lncRNA, NORHA was one of the upregulated lncRNAs identified in the atretic follicles. To determine NORHA function, RT-PCR, flow cytometry and western blotting were performed, and the results showed that NORHA was involved in follicular atresia by influencing GC apoptosis with or without oxidative stress. To determine the mechanism of action, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay were performed, and the results showed that NORHA acted as a ‘sponge’, that directly bound to the miR-183-96-182 cluster, and thus prevented its targeted inhibition of FoxO1, a major sensor and effector of oxidative stress. Conclusions We provide a comprehensive perspective of lncRNA regulation of follicular atresia, and demonstrate that NORHA, a novel lncRNA related to follicular atresia, induces GC apoptosis by influencing the activities of the miR-183-96-182 cluster and FoxO1 axis. |
| first_indexed | 2024-12-17T20:02:18Z |
| format | Article |
| id | doaj.art-86fa63db4e6c4809837dddf0c3facfe2 |
| institution | Directory Open Access Journal |
| issn | 2049-1891 |
| language | English |
| last_indexed | 2024-12-17T20:02:18Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Animal Science and Biotechnology |
| spelling | doaj.art-86fa63db4e6c4809837dddf0c3facfe22022-12-21T21:34:26ZengBMCJournal of Animal Science and Biotechnology2049-18912021-10-0112111710.1186/s40104-021-00626-7NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axisWang Yao0Zengxiang Pan1Xing Du2Jinbi Zhang3Honglin Liu4Qifa Li5College of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityCollege of Animal Science and Technology, Nanjing Agricultural UniversityAbstract Background Follicular atresia has been shown to be strongly associated with a low follicle utilization rate and female infertility, which are regulated by many factors such as microRNAs (miRNAs), which constitute a class of noncoding RNAs (ncRNAs). However, little is known about long noncoding RNAs (lncRNAs), which constitute another ncRNA family that regulate follicular atresia. Results A total of 77 differentially expressed lncRNAs, including 67 upregulated and 10 downregulated lncRNAs, were identified in early atretic follicles compared to healthy follicles by RNA-Sequencing. We characterized a noncoding RNA that was highly expressed in atretic follicles (NORHA). As an intergenic lncRNA, NORHA was one of the upregulated lncRNAs identified in the atretic follicles. To determine NORHA function, RT-PCR, flow cytometry and western blotting were performed, and the results showed that NORHA was involved in follicular atresia by influencing GC apoptosis with or without oxidative stress. To determine the mechanism of action, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay were performed, and the results showed that NORHA acted as a ‘sponge’, that directly bound to the miR-183-96-182 cluster, and thus prevented its targeted inhibition of FoxO1, a major sensor and effector of oxidative stress. Conclusions We provide a comprehensive perspective of lncRNA regulation of follicular atresia, and demonstrate that NORHA, a novel lncRNA related to follicular atresia, induces GC apoptosis by influencing the activities of the miR-183-96-182 cluster and FoxO1 axis.https://doi.org/10.1186/s40104-021-00626-7Follicular atresiaGranulosa cell apoptosisncRNA NORHAOxidative stress |
| spellingShingle | Wang Yao Zengxiang Pan Xing Du Jinbi Zhang Honglin Liu Qifa Li NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis Journal of Animal Science and Biotechnology Follicular atresia Granulosa cell apoptosis ncRNA NORHA Oxidative stress |
| title | NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis |
| title_full | NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis |
| title_fullStr | NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis |
| title_full_unstemmed | NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis |
| title_short | NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis |
| title_sort | norha a novel follicular atresia related lncrna promotes porcine granulosa cell apoptosis via the mir 183 96 182 cluster and foxo1 axis |
| topic | Follicular atresia Granulosa cell apoptosis ncRNA NORHA Oxidative stress |
| url | https://doi.org/10.1186/s40104-021-00626-7 |
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