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Identifying miRNA regulatory mechanisms in preeclampsia by systems biology approaches
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BACKGROUND: Preeclampsia (PE) is the major cause of maternal and fetal morbidity and mortality, affecting 3-8% of all pregnancies around the globe. miRNAs are small, noncoding RNA molecules, which negatively regulate gene expression. Abnormally expressed miRNAs contribute to pregnancy complications such as PE. The aim of our study was to find possible regulatory mechanisms by system biology approaches, which are connected to the pathogenesis of PE. METHODS: We integrated publicly available miRNA and gene expression profiles and created a network from the significant miRNA-mRNA pairs with the help of MAGIA and Cytoscape softwares. Two subnetworks were expanded by adding protein-protein interactions. Differentially expressed miRNAs were identified for the evaluation of their regulatory effect. We analyzed the miRNAs and their targets using different bioinformatics tools and through literature research. RESULTS: Altogether, 52,603 miRNA-mRNA interactions were generated by the MAGIA web tool. The top 250 interactions were visualized and pairs with q < 0.0001 were analyzed, which included 85 nodes and 80 edges signalizing the connections between 52 regulated genes and 33 miRNAs. A total of 11 of the regulated genes are PE related and 9 of them were targeted by multiple miRNAs. A total of 8 miRNAs were associated with PE before, and 13 miRNAs regulated more than 1 mRNA. Hsa-mir-210 was the highest degree node in the network and its role in PE is well established. CONCLUSIONS: We identified several miRNA-mRNA regulatory mechanisms which may contribute to the pathogenesis of PE. Further investigations are needed to validate these miRNA-mRNA interactions and to enlighten the possibilities of developing potential therapeutic targets.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" mtid="10051790"> <a href="/gui2/?type=authors&mode=browse&sel=10051790" target="_blank">Biro, O ✉</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10002497"> <a href="/gui2/?type=authors&mode=browse&sel=10002497" target="_blank">Nagy, B</a> </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10003345"> <a href="/gui2/?type=authors&mode=browse&sel=10003345" target="_blank">Rigo, J Jr</a> </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;3152197" mtid="3152197" target="_blank">Identifying miRNA regulatory mechanisms in preeclampsia by systems biology approaches</a></div> <div class="pub-info"> <span class="journal-title">HYPERTENSION IN PREGNANCY</span> <span class="journal-volume">36</span> : <span class="journal-issue">1</span> <span class="page"> pp. 90-99. , 10 p. </span> <span class="year">(2017)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_PAY" title=" Fizetős "> <a style="color:black" title="10.1080/10641955.2016.1239736" target="_blank" href="https://doi.org/10.1080/10641955.2016.1239736"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000395178800015" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000395178800015"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="84994881549" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-84994881549"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="27835046" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=27835046&dopt=Abstract"> PubMed </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:3152197 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 34</span> | Független: 31 | Függő: 3 | Nem jelölt: 0 | WoS jelölt: 29 | Scopus jelölt: 32 | WoS/Scopus jelölt: 32 | DOI jelölt: 31 </div> </div> </div> </div><div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10051790"><a href="/gui2/?type=authors&mode=browse&sel=10051790" target="_blank">Biro O ✉ (<span class="authorship-author-name">Biró Orsolya</span> <span class="authorAux-mtmt"> Folyadékbiopszia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/I. Sz. Szülészeti és Nőgyógyászati Klinika</span> ; <span class="author-name" mtid="10002497"><a href="/gui2/?type=authors&mode=browse&sel=10002497" target="_blank">Nagy B (<span class="authorship-author-name">Nagy Bálint</span> <span class="authorAux-mtmt"> Molekuláris genetika</span>) </a> </span> <span class="author-affil"><span title="Debreceni Egyetem">DE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Humángenetikai Tanszék</span> ; <span class="author-name" mtid="10003345"><a href="/gui2/?type=authors&mode=browse&sel=10003345" target="_blank">Rigo J Jr (<span class="authorship-author-name">Rigó János</span> <span class="authorAux-mtmt"> Szülészet-nőgyógyászat</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/I. Sz. Szülészeti és Nőgyógyászati Klinika</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse¶ms=publication;3152197" target="_blank">Identifying miRNA regulatory mechanisms in preeclampsia by systems biology approaches</a></div> <div> <span class="journal-title">HYPERTENSION IN PREGNANCY</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1064-1955">1064-1955</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1525-6065">1525-6065</a>)</span>: <span class="journal-volume">36</span> <span class="journal-issue">1</span> <span class="page"> pp 90-99 </span> <span class="year">(2017)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_PAY" title=" Fizetős "> <a style="color:black" title="10.1080/10641955.2016.1239736" target="_blank" href="https://doi.org/10.1080/10641955.2016.1239736"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000395178800015" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000395178800015"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="84994881549" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-84994881549"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="27835046" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=27835046&dopt=Abstract"> PubMed </a> </span> </span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 34</span> | Független: 31 | Függő: 3 | Nem jelölt: 0 | WoS jelölt: 29 | Scopus jelölt: 32 | WoS/Scopus jelölt: 32 | DOI jelölt: 31 </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 3152197</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> <span class="oldId">Régi azonosító: 3152197</span> | Forrás | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">MEDLINE</span> </div> <div class="lastModified">Utolsó módosítás: 2022.11.17. 10:56 Molnár-Taga Márta (SE 4-es admin) </div> </div></div>
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To explore the key genes associated with both PCOS and breast cancer, we overlapped the synchronously differently expressed genes in two obese insulin-resistant GEO datasets in muscle tissue and genes exert essential roles in breast cancer prognosis together base on the following reasons: (1) Androgens excess is believed to contribute to the onset of both PCOS and breast cancer. (2) PCOS is usually complicated with metabolic symptoms, such as obesity and insulin-resistance. (3) Muscle is the main place where energy metabolism and material metabolism take place. Consequently, 53 genes were found, functionally enriched in pathways such as pyruvate metabolism, muscle system process and development of primary male sexual characteristics etc. We further lay our eyes on genes correlated with male sexual characteristics, which may be involved in the onset of both PCOS and breast cancer. Three genes were indicated to be associated with this process, including hydroxysteroid (17-beta) dehydrogenase 4/HSD17B4, platelet-derived growth factor receptor, alpha polypeptide/PDGFRA and high-mobility group box 2/HMGB2. Gene-drug interaction network about the three genes were then constructed. Drugs or chemicals that contribute to correcting the disorder of lipid metabolism were detected to restore the abnormal expression of the three genes in PCOS, such as simvastatin, bezafibrate, fenofibrate et al, which provide further choices for managing patients with PCOS.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" > Xu, H </span> <span class="author-type"> </span> ; <span class="author-name" > Han, Y </span> <span class="author-type"> </span> ; <span class="author-name" > Lou, J </span> <span class="author-type"> </span> ; <span class="author-name" > Zhang, H </span> <span class="author-type"> </span> ; <span class="author-name" > Zhao, Y </span> <span class="author-type"> </span> ; <span class="author-name" mtid="10000109"> <a href="/gui2/?type=authors&mode=browse&sel=10000109" target="_blank">Gyorffy, B</a> </span> <span class="author-type"> </span> ; <span class="author-name" > Li, R ✉ </span> <span class="author-type"> </span> </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;3238399" mtid="3238399" target="_blank">PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian syndrome and breast cancer</a></div> <div class="pub-info"> <span class="journal-title">ONCOTARGET</span> <span class="journal-volume">8</span> : <span class="journal-issue">41</span> <span class="page"> pp. 69520-69526. , 7 p. </span> <span class="year">(2017)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.18632/oncotarget.17846" target="_blank" href="https://doi.org/10.18632/oncotarget.17846"> DOI </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:black" title="6213" target="_blank" href="https://repo.lib.semmelweis.hu/handle/123456789/6213"> SE Repozitórium </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000411153300027" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000411153300027"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85030263065" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85030263065"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="29050221" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=29050221&dopt=Abstract"> PubMed </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Közlemény:3238399 </span> <span class="status-holder"><span class="status-data status-VALIDATED"> Egyeztetett </span></span> <span class="pub-core">Forrás Idéző </span> <span class="pub-type">Folyóiratcikk (Szakcikk ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Tudományos</span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 14</span> | Független: 13 | Függő: 1 | Nem jelölt: 0 | WoS jelölt: 13 | Scopus jelölt: 12 | WoS/Scopus jelölt: 14 | DOI jelölt: 13 </div> </div> </div> </div><div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" >Xu H </span> ; <span class="author-name" >Han Y </span> ; <span class="author-name" >Lou J </span> ; <span class="author-name" >Zhang H </span> ; <span class="author-name" >Zhao Y </span> ; <span class="author-name" mtid="10000109"><a href="/gui2/?type=authors&mode=browse&sel=10000109" target="_blank">Gyorffy B (<span class="authorship-author-name">Győrffy Balázs</span> <span class="authorAux-mtmt"> Onkológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/II. Sz. Gyermekgyógyászati Klinika; <span title="MTA Természettudományi Kutatóközpont">MTA TTK</span>/<span title="Enzimológiai Intézet">EI</span>/Onkológiai Biomarker Kutatócsoport (Lendület)</span> ; <span class="author-name" >Li R ✉ </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse¶ms=publication;3238399" target="_blank">PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian syndrome and breast cancer</a></div> <div> <span class="journal-title">ONCOTARGET</span> <span class="journal-issn">( <a target="_blank" href="https://portal.issn.org/resource/ISSN/1949-2553">1949-2553</a>)</span>: <span class="journal-volume">8</span> <span class="journal-issue">41</span> <span class="page"> pp 69520-69526 </span> <span class="year">(2017)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.18632/oncotarget.17846" target="_blank" href="https://doi.org/10.18632/oncotarget.17846"> DOI </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:black" title="6213" target="_blank" href="https://repo.lib.semmelweis.hu/handle/123456789/6213"> SE Repozitórium </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000411153300027" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000411153300027"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85030263065" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85030263065"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="29050221" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=29050221&dopt=Abstract"> PubMed </a> </span> </span> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 14</span> | Független: 13 | Függő: 1 | Nem jelölt: 0 | WoS jelölt: 13 | Scopus jelölt: 12 | WoS/Scopus jelölt: 14 | DOI jelölt: 13 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;3238399&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 1 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 3238399</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> <span class="oldId">Régi azonosító: 3238399</span> | Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">MEDLINE</span> </div> <div class="lastModified">Utolsó módosítás: 2023.09.05. 09:36 Molnár-Taga Márta (SE 4-es admin) </div> </div></div>