circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion
Unexplained recurrent spontaneous abortion (URSA) is one of the most intractable clinical challenges in reproduction. As a specific type of endogenous non-coding RNA, circular RNAs (circRNAs) have great pre-clinical diagnostic and therapeutic values in diseases. Recently, thousands of circRNAs were...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253121001530 |
| _version_ | 1830453775565848576 |
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| author | Minyue Tang Long Bai Zhe Wan Shan Wan Yu Xiang Yeqing Qian Long Cui Jiali You Xiaoling Hu Fan Qu Yimin Zhu |
| author_facet | Minyue Tang Long Bai Zhe Wan Shan Wan Yu Xiang Yeqing Qian Long Cui Jiali You Xiaoling Hu Fan Qu Yimin Zhu |
| author_sort | Minyue Tang |
| collection | DOAJ |
| description | Unexplained recurrent spontaneous abortion (URSA) is one of the most intractable clinical challenges in reproduction. As a specific type of endogenous non-coding RNA, circular RNAs (circRNAs) have great pre-clinical diagnostic and therapeutic values in diseases. Recently, thousands of circRNAs were detected in human pre-implantation embryos, indicating that circRNAs potentially have important regulatory functions. However, the roles of circRNAs in URSA remain largely unknown. In this study, we elucidated deregulated circRNA expression and distinct competing endogenous RNA (ceRNA) networks by comparing URSA placental villus with that of patients with normal pregnancy using microarrays. We characterized a distinct circRNA, circRNA-0050703, which is downregulated in URSA placental villus (thus we named it circRNA-DURSA). Silencing of circRNA-DURSA results in trophoblast cell apoptosis in vitro. Furthermore, mechanistic dissection revealed that circRNA-DURSA exerts its effects by competitively binding to miR-760, which post-transcriptionally targets HIST1H2BE. Additionally, after circRNA-DURSA silencing in vivo, the numbers of implanted embryos decreased significantly. These results reveal the regulatory roles of circRNA-DURSA in trophoblasts and identified a distinct circRNA-DURSA/miR-760/HIST1H2BE axis as potentially important diagnostic and therapeutic targets for URSA treatment. |
| first_indexed | 2024-12-21T09:16:50Z |
| format | Article |
| id | doaj.art-c7045724a6cc4132811b7368f81b25c0 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-21T09:16:50Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-c7045724a6cc4132811b7368f81b25c02022-12-21T19:09:08ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-12-012614331445circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortionMinyue Tang0Long Bai1Zhe Wan2Shan Wan3Yu Xiang4Yeqing Qian5Long Cui6Jiali You7Xiaoling Hu8Fan Qu9Yimin Zhu10Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Key Laboratory of Reproductive Genetics (Ministry of Education) and Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaKey Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaWomen’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaWomen’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Corresponding author: Fan Qu, PhD, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Corresponding author: Yimin Zhu, PhD, Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.Unexplained recurrent spontaneous abortion (URSA) is one of the most intractable clinical challenges in reproduction. As a specific type of endogenous non-coding RNA, circular RNAs (circRNAs) have great pre-clinical diagnostic and therapeutic values in diseases. Recently, thousands of circRNAs were detected in human pre-implantation embryos, indicating that circRNAs potentially have important regulatory functions. However, the roles of circRNAs in URSA remain largely unknown. In this study, we elucidated deregulated circRNA expression and distinct competing endogenous RNA (ceRNA) networks by comparing URSA placental villus with that of patients with normal pregnancy using microarrays. We characterized a distinct circRNA, circRNA-0050703, which is downregulated in URSA placental villus (thus we named it circRNA-DURSA). Silencing of circRNA-DURSA results in trophoblast cell apoptosis in vitro. Furthermore, mechanistic dissection revealed that circRNA-DURSA exerts its effects by competitively binding to miR-760, which post-transcriptionally targets HIST1H2BE. Additionally, after circRNA-DURSA silencing in vivo, the numbers of implanted embryos decreased significantly. These results reveal the regulatory roles of circRNA-DURSA in trophoblasts and identified a distinct circRNA-DURSA/miR-760/HIST1H2BE axis as potentially important diagnostic and therapeutic targets for URSA treatment.http://www.sciencedirect.com/science/article/pii/S2162253121001530circRNAtrophoblastapoptosisunexplained recurrent spontaneous abortionmiRNA |
| spellingShingle | Minyue Tang Long Bai Zhe Wan Shan Wan Yu Xiang Yeqing Qian Long Cui Jiali You Xiaoling Hu Fan Qu Yimin Zhu circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion Molecular Therapy: Nucleic Acids circRNA trophoblast apoptosis unexplained recurrent spontaneous abortion miRNA |
| title | circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion |
| title_full | circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion |
| title_fullStr | circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion |
| title_full_unstemmed | circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion |
| title_short | circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion |
| title_sort | circrna dursa regulates trophoblast apoptosis via mir 760 hist1h2be axis in unexplained recurrent spontaneous abortion |
| topic | circRNA trophoblast apoptosis unexplained recurrent spontaneous abortion miRNA |
| url | http://www.sciencedirect.com/science/article/pii/S2162253121001530 |
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