Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE

Yetao Xu; Dan Wu; Jie Liu; Shiyun Huang; Qing Zuo; Xi Xia; Ying Jiang; Sailan Wang; Yanzi Chen; Tianjun Wang; Lizhou Sun

doi:10.1016/j.omtn.2018.05.007

Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE

Mol Ther Nucleic Acids. 2018 Sep 7:12:195-206. doi: 10.1016/j.omtn.2018.05.007. Epub 2018 May 29.

Authors

Yetao Xu¹, Dan Wu², Jie Liu³, Shiyun Huang², Qing Zuo², Xi Xia⁴, Ying Jiang⁵, Sailan Wang², Yanzi Chen⁶, Tianjun Wang², Lizhou Sun⁷

Affiliations

¹ Department 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, USA.
² Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
³ Department of Obstetrics and Gynecology and Reproduction Center, Xuzhou Maternity and Child Health Care Hospital, Xuzhou 221000, China.
⁴ Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Shenzhen Hospital, FuTian District, Shenzhen, Guangdong, China.
⁵ Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁶ Department of Emergency, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
⁷ Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. Electronic address: sunlizhou@njmu.edu.cn.

Abstract

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; HOXA7; RND3; preeclampsia; proliferation.