Identifying key genes and drug screening for preeclampsia based on gene expression profiles

Abstract

Preeclampsia (PE) is characterized by gestational hypertension and proteinuria, and is a leading cause of maternal death and perinatal morbidity globally. Although the exact cause of PE remains unclear, several studies have suggested a role for abnormal expression of multiple genes. The aim of the present study was to identify key genes and related pathways, and to screen for drugs that regulate these genes for potential PE therapy. The GSE60438 dataset was acquired from the Gene Expression Omnibus database to analyze differentially expressed genes (DEGs). By constructing a protein-protein interaction network and performing reverse transcription-quantitative PCR verification, proteasome 26S subunit, non-ATPase 14, prostaglandin E synthase 3 and ubiquinol-cytochrome c reductase core protein 2 were identified as key genes in PE. In addition, PE was found to be associated with 'circadian rhythm', 'fatty acid metabolism', 'DNA damage response detection of DNA damage', 'regulation of DNA repair' and 'endothelial cell development'. Through connectivity map analysis of DEGs, furosemide and droperidol were suggested to be therapeutic drugs that may target the hub genes for PE treatment. Results analysis of GSEA were included in the discussion section of this article. In conclusion, the current study identified novel key genes associated with the onset of PE and potential drugs for PE treatment.

Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia

“…Some studies suggested dysregulation of ribosomal pathways in PE [24,25]. Transcriptional profiling of the decidua in PE revealed fatty acid metabolism might play an essential role in pathogenesis [26,27].…”

Hes-related family BHLH transcription factor with YRPW motif 1-activated proteasome 26S subunit, non-ATPase 14 regulates trophoblast function and endometrial angiogenesis

“…Recently, a gene expression profiling study revealed that PSMD14 expression was aberrantly reduced in pregnant women with PE in comparison with healthy pregnant women ( 13 ), suggesting a role for PSMD14 in PE pathogenesis. PSMD14 has been previously reported to be a potential prognostic biomarker and treatment target in several types of cancer, including breast cancer ( 26 ), lung adenocarcinoma ( 27 ) and melanoma ( 28 ).…”

“…It has been recently reported that pregnant women with PE have significantly lower expression levels of proteasome 26S subunit, non-ATPase 14 (PSMD14) in the placenta, compared with those with normal blood pressure ( 13 ). In view of this finding, PSMD14 was proposed to be a key gene in PE with potential prognostic and therapeutic value ( 13 ).…”

“…It has been recently reported that pregnant women with PE have significantly lower expression levels of proteasome 26S subunit, non-ATPase 14 (PSMD14) in the placenta, compared with those with normal blood pressure ( 13 ). In view of this finding, PSMD14 was proposed to be a key gene in PE with potential prognostic and therapeutic value ( 13 ). Furthermore, PSMD14 expression has been previously found to be increased in liver cancer tissues, which promotes the proliferation, migration and invasion of hepatocellular carcinoma cells to facilitate tumor growth in vivo ( 14 ).…”

Neurologic Sequelae Associated with Hypertensive Disorders of Pregnancy

“…Pregnancy-related infections, maternal diabetes, autoimmune disorders, maternal obesity and toxic stresses can be synergistic in the same individual, worsening the adverse effects from HDP as pregnancy advances. Identification of proteomic biomarkers representing genes and related pathways before and during early pregnancy offer the opportunity to develop screening protocols to treat specific forms of HDP, as well as co-morbidities [16]. Depending on the burden of transgenerational heritability, varying degrees of sequalae may subsequently be expressed across generations.…”