Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE
The long noncoding RNA HOXA11-AS displays abnormal expression in numerous human diseases. However, its function and biological mechanisms remain unclear in preeclampsia (PE). In this study, we report that HOXA11-AS is significantly downregulated in preeclamptic placental tissues and could contribute...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-09-01
|
| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253118301045 |
| _version_ | 1818967284853506048 |
|---|---|
| author | Yetao Xu Dan Wu Jie Liu Shiyun Huang Qing Zuo Xi Xia Ying Jiang Sailan Wang Yanzi Chen Tianjun Wang Lizhou Sun |
| author_facet | Yetao Xu Dan Wu Jie Liu Shiyun Huang Qing Zuo Xi Xia Ying Jiang Sailan Wang Yanzi Chen Tianjun Wang Lizhou Sun |
| author_sort | Yetao Xu |
| collection | DOAJ |
| description | The long noncoding RNA HOXA11-AS displays abnormal expression in numerous human diseases. However, its function and biological mechanisms remain unclear in preeclampsia (PE). In this study, we report that HOXA11-AS is significantly downregulated in preeclamptic placental tissues and could contribute to the occurrence and development of PE. Silencing of HOXA11-AS expression could significantly suppress trophoblast cell growth and migration, whereas HOXA11-AS overexpression facilitated cell growth in the HTR-8/SVneo, JEG3, and JAR cell lines. RNA-seq analysis also indicated that HOXA11-AS silencing preferentially regulated numerous genes associated with cell proliferation and cell migration. Mechanistic analyses showed that HOXA11-AS could recruit Ezh2 and Lsd1 protein and regulate RND3 mRNA expression in the nucleus. In the cytoplasm, HOXA11-AS modulates HOXA7 expression by sponged miR-15b-5p, affecting trophoblast cell proliferation. Together, these data confirm that aberrant expression of HOXA11-AS is involved in the occurrence and development of PE and may act as a prospective diagnosis and therapeutic target in PE. Keywords: HOXA11-AS, preeclampsia, proliferation, RND3, HOXA7 |
| first_indexed | 2024-12-20T13:46:21Z |
| format | Article |
| id | doaj.art-a0d9991eea3c4d018d29bf107bb62a09 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-20T13:46:21Z |
| publishDate | 2018-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-a0d9991eea3c4d018d29bf107bb62a092022-12-21T19:38:39ZengElsevierMolecular Therapy: Nucleic Acids2162-25312018-09-0112195206Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PEYetao Xu0Dan Wu1Jie Liu2Shiyun Huang3Qing Zuo4Xi Xia5Ying Jiang6Sailan Wang7Yanzi Chen8Tianjun Wang9Lizhou Sun10Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, ChinaDepartment of Obstetrics and Gynecology and Reproduction Center, Xuzhou Maternity and Child Health Care Hospital, Xuzhou 221000, ChinaDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, ChinaDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, ChinaDepartment of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Shenzhen Hospital, FuTian District, Shenzhen, Guangdong, ChinaDepartment of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, ChinaDepartment of Emergency, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, ChinaDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, ChinaDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China; Corresponding author: Lizhou Sun, Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.The long noncoding RNA HOXA11-AS displays abnormal expression in numerous human diseases. However, its function and biological mechanisms remain unclear in preeclampsia (PE). In this study, we report that HOXA11-AS is significantly downregulated in preeclamptic placental tissues and could contribute to the occurrence and development of PE. Silencing of HOXA11-AS expression could significantly suppress trophoblast cell growth and migration, whereas HOXA11-AS overexpression facilitated cell growth in the HTR-8/SVneo, JEG3, and JAR cell lines. RNA-seq analysis also indicated that HOXA11-AS silencing preferentially regulated numerous genes associated with cell proliferation and cell migration. Mechanistic analyses showed that HOXA11-AS could recruit Ezh2 and Lsd1 protein and regulate RND3 mRNA expression in the nucleus. In the cytoplasm, HOXA11-AS modulates HOXA7 expression by sponged miR-15b-5p, affecting trophoblast cell proliferation. Together, these data confirm that aberrant expression of HOXA11-AS is involved in the occurrence and development of PE and may act as a prospective diagnosis and therapeutic target in PE. Keywords: HOXA11-AS, preeclampsia, proliferation, RND3, HOXA7http://www.sciencedirect.com/science/article/pii/S2162253118301045 |
| spellingShingle | Yetao Xu Dan Wu Jie Liu Shiyun Huang Qing Zuo Xi Xia Ying Jiang Sailan Wang Yanzi Chen Tianjun Wang Lizhou Sun Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE Molecular Therapy: Nucleic Acids |
| title | Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE |
| title_full | Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE |
| title_fullStr | Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE |
| title_full_unstemmed | Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE |
| title_short | Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE |
| title_sort | downregulated lncrna hoxa11 as affects trophoblast cell proliferation and migration by regulating rnd3 and hoxa7 expression in pe |
| url | http://www.sciencedirect.com/science/article/pii/S2162253118301045 |
| work_keys_str_mv | AT yetaoxu downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT danwu downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT jieliu downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT shiyunhuang downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT qingzuo downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT xixia downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT yingjiang downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT sailanwang downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT yanzichen downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT tianjunwang downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe AT lizhousun downregulatedlncrnahoxa11asaffectstrophoblastcellproliferationandmigrationbyregulatingrnd3andhoxa7expressioninpe |