SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1
Abstract Folliculogenesis is a crucial process for production functional female gametes in mammals. The imbalance of apoptosis and proliferation of ovarian granulosa cells has been identified as an important cause for abnormal folliculogenesis. Sex-determining region Y-box protein 3 (SOX3), belonged...
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2025-06-01
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| Series: | Cellular and Molecular Life Sciences |
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| Online Access: | https://doi.org/10.1007/s00018-025-05797-4 |
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| author | Rui Cai Cong Li Wenhui Shi Fenfen Xie Mengmeng Fan Hao Zhang Zhuang Liu Yuanhua Chen Qiang Hong |
| author_facet | Rui Cai Cong Li Wenhui Shi Fenfen Xie Mengmeng Fan Hao Zhang Zhuang Liu Yuanhua Chen Qiang Hong |
| author_sort | Rui Cai |
| collection | DOAJ |
| description | Abstract Folliculogenesis is a crucial process for production functional female gametes in mammals. The imbalance of apoptosis and proliferation of ovarian granulosa cells has been identified as an important cause for abnormal folliculogenesis. Sex-determining region Y-box protein 3 (SOX3), belonged to the SRY-box transcription factor family, is involved in follicular development. Nonetheless, the regulatory mechanisms of SOX3 and ovarian granulosa cell state remains poorly understood. In this study, we constructed stable overexpression and knockdown SOX3 ovarian granulosa cell lines. We observed that SOX3 can promote the proliferation and inhibit the apoptosis of KGN cells. Comparative transcriptome analysis revealed that 1,717 genes exhibited up-regulation and 1,240 genes displayed down-regulation in OE-SOX3 compared to OE-NC. Further pathway analysis demonstrated that the DEGs were associated with many biological processes, particularly the PI3K/AKT signaling pathway. Moreover, we discovered that SOX3 facilitates the proliferation and inhibits the apoptosis of KGN cells through PI3K/AKT signaling pathway. Finally, we unveiled that SOX3 can bind to the promoter of SPP1 and activate the promoter activity, which in turn up-regulates the PI3K/AKT signaling pathway. The results were also confirmed in sox3 knockout zebrafish. Altogether, our findings demonstrated that SOX3 facilitates granulosa cell proliferation and suppresses apoptosis by activating the SPP1/PI3K/AKT pathway, which might be implicated in improving female fecundity. |
| format | Article |
| id | doaj-art-d312358fa32648548c1efa54edbbbe78 |
| institution | Kabale University |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-d312358fa32648548c1efa54edbbbe782025-08-20T03:37:23ZengSpringerCellular and Molecular Life Sciences1420-90712025-06-0182111810.1007/s00018-025-05797-4SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1Rui Cai0Cong Li1Wenhui Shi2Fenfen Xie3Mengmeng Fan4Hao Zhang5Zhuang Liu6Yuanhua Chen7Qiang Hong8School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversitySchool of Basic Medical Sciences, Anhui Medical UniversityAbstract Folliculogenesis is a crucial process for production functional female gametes in mammals. The imbalance of apoptosis and proliferation of ovarian granulosa cells has been identified as an important cause for abnormal folliculogenesis. Sex-determining region Y-box protein 3 (SOX3), belonged to the SRY-box transcription factor family, is involved in follicular development. Nonetheless, the regulatory mechanisms of SOX3 and ovarian granulosa cell state remains poorly understood. In this study, we constructed stable overexpression and knockdown SOX3 ovarian granulosa cell lines. We observed that SOX3 can promote the proliferation and inhibit the apoptosis of KGN cells. Comparative transcriptome analysis revealed that 1,717 genes exhibited up-regulation and 1,240 genes displayed down-regulation in OE-SOX3 compared to OE-NC. Further pathway analysis demonstrated that the DEGs were associated with many biological processes, particularly the PI3K/AKT signaling pathway. Moreover, we discovered that SOX3 facilitates the proliferation and inhibits the apoptosis of KGN cells through PI3K/AKT signaling pathway. Finally, we unveiled that SOX3 can bind to the promoter of SPP1 and activate the promoter activity, which in turn up-regulates the PI3K/AKT signaling pathway. The results were also confirmed in sox3 knockout zebrafish. Altogether, our findings demonstrated that SOX3 facilitates granulosa cell proliferation and suppresses apoptosis by activating the SPP1/PI3K/AKT pathway, which might be implicated in improving female fecundity.https://doi.org/10.1007/s00018-025-05797-4FolliculogenesisSOX3ProliferationApoptosisSPP1PI3K/AKT pathway |
| spellingShingle | Rui Cai Cong Li Wenhui Shi Fenfen Xie Mengmeng Fan Hao Zhang Zhuang Liu Yuanhua Chen Qiang Hong SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1 Cellular and Molecular Life Sciences Folliculogenesis SOX3 Proliferation Apoptosis SPP1 PI3K/AKT pathway |
| title | SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1 |
| title_full | SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1 |
| title_fullStr | SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1 |
| title_full_unstemmed | SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1 |
| title_short | SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1 |
| title_sort | sox3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating pi3k akt pathway by targeting spp1 |
| topic | Folliculogenesis SOX3 Proliferation Apoptosis SPP1 PI3K/AKT pathway |
| url | https://doi.org/10.1007/s00018-025-05797-4 |
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