The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway
Abstract Background Endometriosis cause decreases in life quality and pelvic pain in reproductive-age women. Methylation abnormalities played a functional role in the progression of endometriosis, this study aimed to explore the mechanisms mediated by abnormal methylation in the development of EMS....
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | BMC Molecular and Cell Biology |
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| Online Access: | https://doi.org/10.1186/s12860-023-00470-9 |
| _version_ | 1797853547817074688 |
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| author | Mei Yang Lin Li Xiaojie Huang Hui Xing Li Hong Chunfan Jiang |
| author_facet | Mei Yang Lin Li Xiaojie Huang Hui Xing Li Hong Chunfan Jiang |
| author_sort | Mei Yang |
| collection | DOAJ |
| description | Abstract Background Endometriosis cause decreases in life quality and pelvic pain in reproductive-age women. Methylation abnormalities played a functional role in the progression of endometriosis, this study aimed to explore the mechanisms mediated by abnormal methylation in the development of EMS. Materials and methods Next-generation sequencing dataset and methylation profiling dataset were used to screen out the key gene SFRP2. Western bolt, Real-time PCR, Aza-2?deoxycytidine treatment, luciferase reporter assay, Methylation-specific PCR , Bisulfite sequencing PCR and lentivirus infection were carried out to detect the methylation status and signaling pathway with the primary epithelial cells. Transwell assay and wound scratch assay were implemented to observe the differences of migration ability with the intervening with the expression of SFRP2. Results To define the role of the DNA methylation-regulated genes in the pathogenesis of EMS, we performed both DNA methylomic and expression analyses of ectopic endometrium and ectopic endometrium epithelial cells(EEECs) and found that SFRP2 is demethylated/upregulated in ectopic endometrium and EEECs. The expression of lentivirus carrying SFRP2 cDNA up-regulates the activity of Wnt signaling and the protein expression of ?-catenin in EEECs. SFRP2 impact on the invasion and migration of ectopic endometrium by modulating the activities of the Wnt/?-catenin signaling pathway. The invasion and migration ability of EEECs were significantly strengthened after demethylation treatment including 5-Aza and the knockdown of DNMT1. Conclusion In summary, the increased SFRP2 expression-induced Wnt/?-catenin signaling due to the demethylation of the SFRP2 promoter plays an important role in the pathogenesis of EMS, suggesting that SFRP2 might be a therapeutic target for EMS treatment. |
| first_indexed | 2024-04-09T19:52:25Z |
| format | Article |
| id | doaj.art-ccd32feece9a475f84d0e79948babe18 |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-04-09T19:52:25Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-ccd32feece9a475f84d0e79948babe182023-04-03T05:44:15ZengBMCBMC Molecular and Cell Biology2661-88502023-03-0124111410.1186/s12860-023-00470-9The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathwayMei Yang0Lin Li1Xiaojie Huang2Hui Xing3Li Hong4Chunfan Jiang5Department of Obstetrics and Gynecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and ScienceDepartment of Obstetrics and Gynecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and ScienceDepartment of Obstetrics and Gynecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and ScienceDepartment of Obstetrics and Gynecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and ScienceDepartment of Obstetrics and Gynecology, Renmin Hospital of Wuhan UniversityDepartment of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and ScienceAbstract Background Endometriosis cause decreases in life quality and pelvic pain in reproductive-age women. Methylation abnormalities played a functional role in the progression of endometriosis, this study aimed to explore the mechanisms mediated by abnormal methylation in the development of EMS. Materials and methods Next-generation sequencing dataset and methylation profiling dataset were used to screen out the key gene SFRP2. Western bolt, Real-time PCR, Aza-2?deoxycytidine treatment, luciferase reporter assay, Methylation-specific PCR , Bisulfite sequencing PCR and lentivirus infection were carried out to detect the methylation status and signaling pathway with the primary epithelial cells. Transwell assay and wound scratch assay were implemented to observe the differences of migration ability with the intervening with the expression of SFRP2. Results To define the role of the DNA methylation-regulated genes in the pathogenesis of EMS, we performed both DNA methylomic and expression analyses of ectopic endometrium and ectopic endometrium epithelial cells(EEECs) and found that SFRP2 is demethylated/upregulated in ectopic endometrium and EEECs. The expression of lentivirus carrying SFRP2 cDNA up-regulates the activity of Wnt signaling and the protein expression of ?-catenin in EEECs. SFRP2 impact on the invasion and migration of ectopic endometrium by modulating the activities of the Wnt/?-catenin signaling pathway. The invasion and migration ability of EEECs were significantly strengthened after demethylation treatment including 5-Aza and the knockdown of DNMT1. Conclusion In summary, the increased SFRP2 expression-induced Wnt/?-catenin signaling due to the demethylation of the SFRP2 promoter plays an important role in the pathogenesis of EMS, suggesting that SFRP2 might be a therapeutic target for EMS treatment.https://doi.org/10.1186/s12860-023-00470-9SFRP2EndometriosisWnt pathwayDemethylation |
| spellingShingle | Mei Yang Lin Li Xiaojie Huang Hui Xing Li Hong Chunfan Jiang The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway BMC Molecular and Cell Biology SFRP2 Endometriosis Wnt pathway Demethylation |
| title | The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway |
| title_full | The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway |
| title_fullStr | The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway |
| title_full_unstemmed | The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway |
| title_short | The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway |
| title_sort | dna demethylation regulated sfrp2 dictates the progression of endometriosis via activation of the wnt β catenin signaling pathway |
| topic | SFRP2 Endometriosis Wnt pathway Demethylation |
| url | https://doi.org/10.1186/s12860-023-00470-9 |
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