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The pseudogene URAHP promotes proliferation and regulates the pathogenesis of preeclampsia.

ABSTRACT: 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.

SUBMITTER: Li W

PROVIDER: S-EPMC7476166 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The pseudogene URAHP promotes proliferation and regulates the pathogenesis of preeclampsia.

Li Weiwei W Li Yanshu Y

American journal of translational research 20200815 8

<h4>Objectives</h4>Preeclampsia (PE), a pregnancy-specific disorder characterized by hypertension and a variety of organ failures, currently lacks effective treatments. Urate (hydroxyiso-) hydrolase, pseudogene (<i>URAHP</i>), 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.<h4>Methods</h4>Placentae were divided into two groups: those from patients with norm ...[more]

PMID: 32913544

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Project description:BackgroundRecent studies have shown that the abnormal expression of long-chain non-coding RNAs (lncRNAs) can significantly affect the biological function of trophoblast cells and lead to the occurrence of preeclampsia (PE). This study explores the expression of lncRNA LINC00922 in PE and its effect on the function of placental trophoblast cells, along with the corresponding molecular mechanism, providing a theoretical basis and molecular target for understanding the occurrence, early diagnosis, and targeted therapy of PE.MethodsFluorescence quantitative PCR was used to detect the expression of LINC00922 in 30 cases of PE tissues and normal tissues. The CCK-8 assay, clone formation experiment, and flow cytometry were used to detect the effects of LINC00922 knockdown or overexpression on the proliferation, colony formation, and cell cycle of HTR-8/SVneo placental trophoblast cells. The Transwell assay was used to detect the effects of LINC00922 knockdown or overexpression on the invasion and migration of HTR 8/SVneo cells, and western blot was used to detect the expression of cell cycle-related proteins and invasion and migration-related proteins.ResultsLINC00922 was highly expressed in PE tissues. Knockdown of LINC00922 significantly inhibited the proliferation, invasion, and migration of HTR-8/SVneo cells, along with colony formation and the ability to induce cell cycle arrest in the G0/G1 phase. However, overexpression of LINC00922 had the opposite effect. Knockdown or overexpression of LINC00922 significantly affected the expression of cell cycle-related proteins cyclin-dependent kinase 2 (CDK2), G1/S-specific cyclin-D1 (Cyclin D1), p21, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase 9 (MMP-9), vimentin, and E-cadherin, but had no significant effect on the expression of matrix metallopeptidase 2 (MMP-2).ConclusionsLINC00922 was highly expressed in PE, and functional experiments showed that LINC00922 could significantly affect the proliferation and invasion abilities of placental trophoblast cells, suggesting that LINC00922 may play an important role in the occurrence, early diagnosis, and treatment of PE.

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The pseudogene URAHP promotes proliferation and regulates the pathogenesis of preeclampsia.

Publications

The pseudogene URAHP promotes proliferation and regulates the pathogenesis of preeclampsia.

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