lncRNA HIF1A Antisense RNA 2 Modulates Trophoblast Cell Invasion and Proliferation through Upregulating PHLDA1 Expression

Dan Wu; Nana Yang; Yetao Xu; Sailan Wang; Yuanyuan Zhang; Matthew Sagnelli; Bingqing Hui; Zhenyao Huang; Lizhou Sun

doi:10.1016/j.omtn.2019.04.009

lncRNA HIF1A Antisense RNA 2 Modulates Trophoblast Cell Invasion and Proliferation through Upregulating PHLDA1 Expression

Mol Ther Nucleic Acids. 2019 Jun 7:16:605-615. doi: 10.1016/j.omtn.2019.04.009. Epub 2019 Apr 18.

Authors

Dan Wu¹, Nana Yang², Yetao Xu², Sailan Wang², Yuanyuan Zhang², Matthew Sagnelli³, Bingqing Hui⁴, Zhenyao Huang⁵, Lizhou Sun⁶

Affiliations

¹ Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China; Department of Neurobiology, Care Science and Society, Karolinska Institutet, Solna 17177, Sweden.
² Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
³ University of Connecticut School of Medicine, Farmington, CT 06030, USA.
⁴ Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China.
⁵ Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
⁶ Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. Electronic address: lizhou_sun@163.com.

Abstract

Long noncoding RNAs (lncRNAs) have been reported to be involved in various human diseases, and increasing studies have revealed that lncRNAs can play a vital role in preeclampsia (PE). In our study, lncRNA hypoxia-inducible factor 1 alpha (HIF1A) antisense RNA 2 (HIF1A-AS2) was found to be significantly downregulated in placenta tissues of PE patients by quantitative real-time PCR analysis. Moreover, Cell Counting Kit-8 (CCK-8) assays showed that downregulation of HIF1A-AS2 can impede cell proliferation of HTR-8/SVneo and JAR trophoblasts cells. Ectopic overexpression of HIF1A-AS2 can increase the function of trophoblasts cell migration and invasion in vitro. RNA-sequencing (RNA-seq), RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) experiments showed that HIF1A-AS2 can recruit lysine-specific demethylase 1 (LSD1) and epigenetically repress pleckstrin homology-like domain, family A, member 1 (PHLDA1) transcription in human trophoblasts cells. In summary, our findings suggest that downregulated HIF1A-AS2 may play a role in the pathogenesis and progression of PE, and has potential as a novel prognostic marker in PE.

Keywords: HIF1A-AS2; LSD1; PHLDA1; invasion; preeclampsia; proliferation.