Search

The exact mechanism of preeclampsia (PE) remains unclear, accumulating researches have indicated multiple epigenetic factors relate to PE and histone methylation plays a crucial role in modifying the gene expression. So we aimed to confirm that abnormal expression of histone demethylase JHDM1D contributes to PE and lower expression of HLA-G in PE. We tested the expression of JHDM1D, H3K9me2, and H3K27me2 in the placentas of PE and normal control (NC)women who had a healthy pregnancy with Immunohistochemistry and we found that JHDM1D, H3K9me2, and H3K27me2 were all mainly expressed in the nuclei of the extra-villous trophoblasts (EVTs). JHDM1D was lower expressed in PE than in NC placentas, corresponding with the mRNA level and protein level with qTR-PCR and western blot, while H3K9me2 and H3K27me2 were higher expressed in PE. We further investigated the biological functions of JHDM1D in HTR-8/SVneo cells. We found that siJHDM1D inhibited cell growth after 24 h of the transfection and reduced the invasion, while increasing the apoptosis of HTR-8/SVneo. We then constructed the siJHDM1D stable cell line and confirmed with CHIP-qPCR that siJHDM1D inhibited the expression of HLA-G through increased the enrichment of H3K9me2 and H3K27me2 in the JHDM1D bounding region of HLA-G. Taken together, our study confirms that decreased expression of JHDM1D is associated with PE through down-regulating HLA-G and casts new light to the diagnosis and therapy of PE.

Preeclampsia (PE) is a common pregnancy complication, and placental hypoxia is one of its causes. We aimed to identify the transcriptional profile and construct a long non-coding RNAs (lncRNA)-centered competing endogenous RNAs (ceRNA) network in hypoxia-induced HTR8/SVneo cells. We used datasets from the GEO database to identify important pathways in PE. We performed microarray profiling and functional analysis to identify differentially expressed long non-coding RNAs (lncRNAs), differentially expressed profiles of microRNA (miRNAs), and differentially expressed profiles of messenger RNA (mRNAs) in hypoxia-induced HTR8/SVneo cells. The candidates were validated using quantitative reverse transcription polymerase chain reaction. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were performed to understand the functional significance of differentially expressed genes. Finally, we constructed an lncRNA-centered ceRNA network. Several hub genes were validated both in placentas from PE and normal pregnancy, and in hypoxia-induced HTR8/SVneo cells. The hypoxic response pathway was involved in the pathophysiology of PE. Subsequently, we identified 536 differentially expressed profiles of lncRNAs (183 upregulated and 353 downregulated), 46 differentially expressed profiles of miRNAs (35 upregulated and 11 downregulated), and 2782 differentially expressed profiles of mRNAs (DEmRNAs) (1031 upregulated and 1751 downregulated) in hypoxia-induced HTR8/SVneo cells. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed potential pathways affected by these genes, such as angiogenesis, the HIF-1 signaling pathway, and the PI3K-Akt signaling pathway. The ceRNA network comprised 35 lncRNAs, 11 miRNAs, 27 mRNAs, and 2 hub lncRNAs, which might play a vital role in placental functions and PE. Our results revealed the transcriptome profile and constructed an lncRNA-centered ceRNA network in hypoxia-induced HTR8/SVneo cells, thereby providing potential therapeutic targets for PE.