SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome
IntroductionPolycystic ovary syndrome (PCOS) is characterized by follicular dysplasia, with granulosa cells (GCs) glycolysis playing a pivotal role in this pathology. Although the involvement of long noncoding RNAs (lncRNAs) in diverse biological processes of PCOS has been well documented, the molec...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1585987/full |
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| author | Sisi Yan Bing Qu Yu Chen Qiuji Wu Jinli Ding Hui Qiu |
| author_facet | Sisi Yan Bing Qu Yu Chen Qiuji Wu Jinli Ding Hui Qiu |
| author_sort | Sisi Yan |
| collection | DOAJ |
| description | IntroductionPolycystic ovary syndrome (PCOS) is characterized by follicular dysplasia, with granulosa cells (GCs) glycolysis playing a pivotal role in this pathology. Although the involvement of long noncoding RNAs (lncRNAs) in diverse biological processes of PCOS has been well documented, the molecular mechanism of lncRNA small nucleolar RNA host gene 12 (SNHG12) in PCOS remains unclear.MethodsIn this study, we measured SNHG12 expression in GCs of PCOS patients and healthy controls using RT-PCR and performed correlation analysis between SNHG12 expression and glycolytic markers. Using granulosa-like tumor (KGN) cells, we investigated glycolytic capacity and examined the relationship among SNHG12, PTEN and HMGB1 through RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays. Finally, DHEA-induced PCOS mice was constructed using SNHG12 adenovirus to explore its role in PCOS.ResultsSNHG12 expression was significantly downregulated in GCs from PCOS patients compared with healthy controls, and showed positive correlation with glycolytic markers. Functional studies demonstrated that SNHG12 knockdown impaired glycolysis in KGN cells, while SNHG12 overexpression partially restored glycolysis. Furthermore, SNHG12-induced glycolysis affected apoptosis of KGN cells, which mediated follicular dysplasia through lactate production and apoptotic pathways. In vivo, adenovirus-mediated SNHG12 overexpression alleviated the symptoms of PCOS mice. Mechanistically, RIP and ChIP assays revealed that SNHG12 interacts with HMGB1 and inhibits PTEN transcription by preventing HMGB1 from binding to the PTEN promoter, thereby promoting glycolysis in KGN cells.ConclusionOur findings collectively demonstrate that the SNHG12/HMGB1/PTEN axis serves as a novel regulatory mechanism in PCOS by modulating glycolytic-mediated follicular dysplasia in GCs, offering a potential therapeutic target for PCOS. |
| format | Article |
| id | doaj-art-1005ea63bd654f5cb322fe8c74d5a2d8 |
| institution | DOAJ |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-1005ea63bd654f5cb322fe8c74d5a2d82025-08-20T03:13:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-05-011310.3389/fcell.2025.15859871585987SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndromeSisi Yan0Bing Qu1Yu Chen2Qiuji Wu3Jinli Ding4Hui Qiu5Hubei Key Laboratory of Tumor Biological Behaviors, Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaReproductive Medicine Center, Wuhan Children’s Hopital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, ChinaReproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Department of Radiation and Medical Oncology, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, ChinaIntroductionPolycystic ovary syndrome (PCOS) is characterized by follicular dysplasia, with granulosa cells (GCs) glycolysis playing a pivotal role in this pathology. Although the involvement of long noncoding RNAs (lncRNAs) in diverse biological processes of PCOS has been well documented, the molecular mechanism of lncRNA small nucleolar RNA host gene 12 (SNHG12) in PCOS remains unclear.MethodsIn this study, we measured SNHG12 expression in GCs of PCOS patients and healthy controls using RT-PCR and performed correlation analysis between SNHG12 expression and glycolytic markers. Using granulosa-like tumor (KGN) cells, we investigated glycolytic capacity and examined the relationship among SNHG12, PTEN and HMGB1 through RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays. Finally, DHEA-induced PCOS mice was constructed using SNHG12 adenovirus to explore its role in PCOS.ResultsSNHG12 expression was significantly downregulated in GCs from PCOS patients compared with healthy controls, and showed positive correlation with glycolytic markers. Functional studies demonstrated that SNHG12 knockdown impaired glycolysis in KGN cells, while SNHG12 overexpression partially restored glycolysis. Furthermore, SNHG12-induced glycolysis affected apoptosis of KGN cells, which mediated follicular dysplasia through lactate production and apoptotic pathways. In vivo, adenovirus-mediated SNHG12 overexpression alleviated the symptoms of PCOS mice. Mechanistically, RIP and ChIP assays revealed that SNHG12 interacts with HMGB1 and inhibits PTEN transcription by preventing HMGB1 from binding to the PTEN promoter, thereby promoting glycolysis in KGN cells.ConclusionOur findings collectively demonstrate that the SNHG12/HMGB1/PTEN axis serves as a novel regulatory mechanism in PCOS by modulating glycolytic-mediated follicular dysplasia in GCs, offering a potential therapeutic target for PCOS.https://www.frontiersin.org/articles/10.3389/fcell.2025.1585987/fullSNHG12PCOSgranulosa cellsglycolysisfollicular dysplasiaHMGB1 |
| spellingShingle | Sisi Yan Bing Qu Yu Chen Qiuji Wu Jinli Ding Hui Qiu SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome Frontiers in Cell and Developmental Biology SNHG12 PCOS granulosa cells glycolysis follicular dysplasia HMGB1 |
| title | SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome |
| title_full | SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome |
| title_fullStr | SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome |
| title_full_unstemmed | SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome |
| title_short | SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome |
| title_sort | snhg12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome |
| topic | SNHG12 PCOS granulosa cells glycolysis follicular dysplasia HMGB1 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1585987/full |
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