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

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: preeclampsia, HIF1A-AS2, LSD1, proliferation, invasion, PHLDA1