The pseudogene URAHP promotes proliferation and regulates the pathogenesis of preeclampsia

Objectives: Preeclampsia (PE), a pregnancy-specific disorder characterized by hypertension and a variety of organ failures, currently lacks effective treatments. Urate (hydroxyiso-) hydrolase, pseudogene (URAHP), which is also a long noncoding RNA (lncRNA), has higher expression in PE placentae than in normal controls and therefore acquires an investigation for the specific mechanism of regulation.

Methods: Placentae were divided into two groups: those from patients with normal pregnancy (NP) (n = 3) and those from patients with PE (n = 3). Total RNA was extracted from the placentae and differentially expressed lncRNAs and mRNAs in PE and NP were identified by Arraystar Human LncRNA Expression Microarray V4.0 analysis. The microarray data were validated by profiling the noncoding RNA expression of URAHP in NP and PE placental tissues through quantitative real-time PCR (qRT-PCR). Then, we uncover the effect of URAHP on cell proliferation by CCK-8 assay and by 3D colony forming assay. Gene coexpression analysis was conducted to identify mRNAs coexpressed with URAHP. qRT-PCR and western blotting assays were used to measure the expression levels of URAHP and KISS1R in JAR and JET-3 cell lines.

Results: A total of 675 differentially expressed lncRNAs (DELRs) [184 upregulated DELRs and 491 downregulated DELRs] and a total of 205 differently expressed genes (DEGs) [56 upregulated mRNAs and 149 downregulated mRNAs] were finally identified between PE and NP samples through high-throughput sequencing analysis. The expression of lncRNA URAHP was increased significantly in the placentae of women with preeclampsia when compared to those with normal pregnancies. The functional assay suggested that the downregulation of URAHP alters the proliferative capacity of JAR/JET-3 cells and that the overexpression of URAHP promotes the proliferation of HTR-8/SVneo cells. We also determined that URAHP and KISS1R are coexpressed.

Conclusion: We demonstrated for the first time that the pseudogene URAHP may be associated with PE. The results of this study provide a new target for the comprehensive treatment of preeclampsia.