MiRNA-494 induces trophoblast senescence by targeting SIRT1
Objective Although the mechanism underlying preeclampsia (PE) has been widely explored, the mechanisms related to senescence have not yet been fully revealed. Therefore, we investigated the role of the miR-494/longevity protein Sirtuin 1 (SIRT1) axis in PE. Methods Human placental tissue was obtaine...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Hypertension in Pregnancy |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10641955.2023.2219774 |
| _version_ | 1797681515013865472 |
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| author | Sha Su Linlin Zhong Shijin Huang Lingjie Deng Lihong Pang |
| author_facet | Sha Su Linlin Zhong Shijin Huang Lingjie Deng Lihong Pang |
| author_sort | Sha Su |
| collection | DOAJ |
| description | Objective Although the mechanism underlying preeclampsia (PE) has been widely explored, the mechanisms related to senescence have not yet been fully revealed. Therefore, we investigated the role of the miR-494/longevity protein Sirtuin 1 (SIRT1) axis in PE. Methods Human placental tissue was obtained from severe preeclampsia (SPE) (n = 20) and gestational age-matched normotensive pregnancies (n = 20), and senescence-associated β-galactosidase (SAβG) and SIRT1 expression levels were measured. The TargetScan and miRDB databases predicted candidate miRNAs targeting SIRT1, and intersected with differentially expressed miRNAs in the GSE15789 dataset (p < 0.05, |log2FC|≥1.5). Subsequently, we showed that miRNA (miR)-494 expression was significantly elevated in SPE, revealing miR-494 as a candidate SIRT1-binding miRNA. A dual-luciferase assay confirmed the targeting relationship between miR-494 and SIRT1. The senescence phenotype, migration, cell viability, reactive oxygen species (ROS) production levels and inflammatory molecule expression levels were measured after miR-494 expression was altered. We conducted a rescue experiment using SIRT1 plasmids to further demonstrate the regulatory relationship. Results SIRT1 expression was lower(p < 0.01) and miR-494 expression was higher (p < 0.001) in SPE, and SaβG staining showed premature placental aging in SPE (p < 0.001). Dual-luciferase reporter assays revealed that miR-494 targeted SIRT1. Compared to control cells, HTR-8/SVneo cells with upregulation of miR-494 had remarkably downregulated SIRT1 expression (p < 0.001), more SAβG-positive cells (p < 0.001), cell cycle arrested (p < 0.05), and upregulated P21 and P16 expression (p < 0.01). miR-494 overexpression also decreased HTR-8/SVneo cell migration (p < 0.05) and ATP synthesis (p < 0.001), increased ROS levels (p < 0.001), and upregulated NLRP3 and IL-1β expression (p < 0.01). SIRT1-overexpressing plasmids partially reversed the effects of miR-494 overexpression in HTR-8/SVneo cells. Conclusion The miR-494/SIRT1 interaction plays a role in the mechanism of premature placental aging in PE patients. |
| first_indexed | 2024-03-11T23:45:57Z |
| format | Article |
| id | doaj.art-610d5bcf328e40d386adebf645140a85 |
| institution | Directory Open Access Journal |
| issn | 1064-1955 1525-6065 |
| language | English |
| last_indexed | 2024-03-11T23:45:57Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Hypertension in Pregnancy |
| spelling | doaj.art-610d5bcf328e40d386adebf645140a852023-09-19T09:24:44ZengTaylor & Francis GroupHypertension in Pregnancy1064-19551525-60652023-12-0142110.1080/10641955.2023.22197742219774MiRNA-494 induces trophoblast senescence by targeting SIRT1Sha Su0Linlin Zhong1Shijin Huang2Lingjie Deng3Lihong Pang4The First Affiliated Hospital of Guangxi Medical UniversityThe First Affiliated Hospital of Guangxi Medical UniversityThe Second Affiliated Hospital of Guangxi Medical UniversityThe First Affiliated Hospital of Guangxi Medical UniversityThe First Affiliated Hospital of Guangxi Medical UniversityObjective Although the mechanism underlying preeclampsia (PE) has been widely explored, the mechanisms related to senescence have not yet been fully revealed. Therefore, we investigated the role of the miR-494/longevity protein Sirtuin 1 (SIRT1) axis in PE. Methods Human placental tissue was obtained from severe preeclampsia (SPE) (n = 20) and gestational age-matched normotensive pregnancies (n = 20), and senescence-associated β-galactosidase (SAβG) and SIRT1 expression levels were measured. The TargetScan and miRDB databases predicted candidate miRNAs targeting SIRT1, and intersected with differentially expressed miRNAs in the GSE15789 dataset (p < 0.05, |log2FC|≥1.5). Subsequently, we showed that miRNA (miR)-494 expression was significantly elevated in SPE, revealing miR-494 as a candidate SIRT1-binding miRNA. A dual-luciferase assay confirmed the targeting relationship between miR-494 and SIRT1. The senescence phenotype, migration, cell viability, reactive oxygen species (ROS) production levels and inflammatory molecule expression levels were measured after miR-494 expression was altered. We conducted a rescue experiment using SIRT1 plasmids to further demonstrate the regulatory relationship. Results SIRT1 expression was lower(p < 0.01) and miR-494 expression was higher (p < 0.001) in SPE, and SaβG staining showed premature placental aging in SPE (p < 0.001). Dual-luciferase reporter assays revealed that miR-494 targeted SIRT1. Compared to control cells, HTR-8/SVneo cells with upregulation of miR-494 had remarkably downregulated SIRT1 expression (p < 0.001), more SAβG-positive cells (p < 0.001), cell cycle arrested (p < 0.05), and upregulated P21 and P16 expression (p < 0.01). miR-494 overexpression also decreased HTR-8/SVneo cell migration (p < 0.05) and ATP synthesis (p < 0.001), increased ROS levels (p < 0.001), and upregulated NLRP3 and IL-1β expression (p < 0.01). SIRT1-overexpressing plasmids partially reversed the effects of miR-494 overexpression in HTR-8/SVneo cells. Conclusion The miR-494/SIRT1 interaction plays a role in the mechanism of premature placental aging in PE patients.http://dx.doi.org/10.1080/10641955.2023.2219774preeclampsiasirt1mirna-494cellular senescence |
| spellingShingle | Sha Su Linlin Zhong Shijin Huang Lingjie Deng Lihong Pang MiRNA-494 induces trophoblast senescence by targeting SIRT1 Hypertension in Pregnancy preeclampsia sirt1 mirna-494 cellular senescence |
| title | MiRNA-494 induces trophoblast senescence by targeting SIRT1 |
| title_full | MiRNA-494 induces trophoblast senescence by targeting SIRT1 |
| title_fullStr | MiRNA-494 induces trophoblast senescence by targeting SIRT1 |
| title_full_unstemmed | MiRNA-494 induces trophoblast senescence by targeting SIRT1 |
| title_short | MiRNA-494 induces trophoblast senescence by targeting SIRT1 |
| title_sort | mirna 494 induces trophoblast senescence by targeting sirt1 |
| topic | preeclampsia sirt1 mirna-494 cellular senescence |
| url | http://dx.doi.org/10.1080/10641955.2023.2219774 |
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