AUTHOR=Wang Yajuan , Bai Xuening , Guo Xin , Gao Xiaoli , Chen Yuanyuan , Li Huanrong , Fan Wenjun , Han Cha 

TITLE=Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia

JOURNAL=Frontiers in Physiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1031950

DOI=10.3389/fphys.2022.1031950

ISSN=1664-042X

ABSTRACT=<p><bold>Introduction:</bold> Preeclampsia (PE) is a gestational hypertensive disease with unclear pathogenesis. This study aimed to identify the genes that play an important role in determining the pathogenesis of PE using bioinformatics analysis and fundamental researches.</p><p><bold>Materials and methods:</bold> Datasets from the Gene Expression Omnibus (GEO) database were used to screen for differentially expressed genes (DEGs). The NCBI, SangerBox, and other databases were used to analyze the functions of the DEGs. Targetscan7, miRWalk, ENCORI, DIANA TOOLS, CircBank databases, and the Cytoscape tool were used to construct the lncRNA/circRNA-miRNA- <italic>LEP</italic> network. SRAMP, RPISeq, RBPsuite, and catRPAID were used to analyze the RNA modifications of <italic>LEP</italic>. Immune cell infiltration was analyzed using the dataset GSE75010. Placental tissues from normal pregnant women and PE patients were collected, screened for gene expression using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. The results were further verified in HTR-8/SVneo cell line hypoxia model and PE mouse model.</p><p><bold>Results:</bold> Our analyses revealed that <italic>LEP</italic> was significantly upregulated in eight datasets. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that <italic>LEP</italic> was involved in the JAK/STAT signaling pathway, angiogenesis, and placental development. Immune cell infiltration analysis showed that M1 and M2 macrophages differed between normal pregnancies and those in PE patients. A competing endogenous RNA (ceRNA) network was constructed, and proteins interacting with <italic>LEP</italic> were identified. RNA modification sites of <italic>LEP</italic> were also identified. Finally, the overexpression of <italic>LEP</italic> in PE was confirmed in clinical samples, HTR-8/SVneo cell line and PE mouse model.</p><p><bold>Conclusion:</bold> Our results indicate that <italic>LEP</italic> overexpression is associated with PE and may be a potential diagnostic marker and therapeutic target.</p>