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

Introduction: 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.Materials and methods: Datasets from the...

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Main Authors: Yajuan Wang, Xuening Bai, Xin Guo, Xiaoli Gao, Yuanyuan Chen, Huanrong Li, Wenjun Fan, Cha Han
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2022.1031950/full
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author Yajuan Wang
Yajuan Wang
Xuening Bai
Xuening Bai
Xin Guo
Xin Guo
Xiaoli Gao
Xiaoli Gao
Yuanyuan Chen
Yuanyuan Chen
Huanrong Li
Huanrong Li
Wenjun Fan
Wenjun Fan
Cha Han
Cha Han
author_facet Yajuan Wang
Yajuan Wang
Xuening Bai
Xuening Bai
Xin Guo
Xin Guo
Xiaoli Gao
Xiaoli Gao
Yuanyuan Chen
Yuanyuan Chen
Huanrong Li
Huanrong Li
Wenjun Fan
Wenjun Fan
Cha Han
Cha Han
author_sort Yajuan Wang
collection DOAJ
description Introduction: 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.Materials and methods: 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- LEP network. SRAMP, RPISeq, RBPsuite, and catRPAID were used to analyze the RNA modifications of LEP. 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.Results: Our analyses revealed that LEP was significantly upregulated in eight datasets. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that LEP 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 LEP were identified. RNA modification sites of LEP were also identified. Finally, the overexpression of LEP in PE was confirmed in clinical samples, HTR-8/SVneo cell line and PE mouse model.Conclusion: Our results indicate that LEP overexpression is associated with PE and may be a potential diagnostic marker and therapeutic target.
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spelling doaj.art-e757b863a12545358a2e8141d12653e52023-01-04T19:19:01ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-01-011310.3389/fphys.2022.10319501031950Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsiaYajuan Wang0Yajuan Wang1Xuening Bai2Xuening Bai3Xin Guo4Xin Guo5Xiaoli Gao6Xiaoli Gao7Yuanyuan Chen8Yuanyuan Chen9Huanrong Li10Huanrong Li11Wenjun Fan12Wenjun Fan13Cha Han14Cha Han15Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, ChinaIntroduction: 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.Materials and methods: 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- LEP network. SRAMP, RPISeq, RBPsuite, and catRPAID were used to analyze the RNA modifications of LEP. 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.Results: Our analyses revealed that LEP was significantly upregulated in eight datasets. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that LEP 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 LEP were identified. RNA modification sites of LEP were also identified. Finally, the overexpression of LEP in PE was confirmed in clinical samples, HTR-8/SVneo cell line and PE mouse model.Conclusion: Our results indicate that LEP overexpression is associated with PE and may be a potential diagnostic marker and therapeutic target.https://www.frontiersin.org/articles/10.3389/fphys.2022.1031950/fullleptinpreeclampsiaimmune infiltrationbioinformaticscompeting endogenous RNAN 6-methyladenosine
spellingShingle Yajuan Wang
Yajuan Wang
Xuening Bai
Xuening Bai
Xin Guo
Xin Guo
Xiaoli Gao
Xiaoli Gao
Yuanyuan Chen
Yuanyuan Chen
Huanrong Li
Huanrong Li
Wenjun Fan
Wenjun Fan
Cha Han
Cha Han
Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia
Frontiers in Physiology
leptin
preeclampsia
immune infiltration
bioinformatics
competing endogenous RNA
N 6-methyladenosine
title Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia
title_full Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia
title_fullStr Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia
title_full_unstemmed Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia
title_short Bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia
title_sort bioinformatics analysis combined with clinical sample screening reveals that leptin may be a biomarker of preeclampsia
topic leptin
preeclampsia
immune infiltration
bioinformatics
competing endogenous RNA
N 6-methyladenosine
url https://www.frontiersin.org/articles/10.3389/fphys.2022.1031950/full
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