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Micro-RNA signatures in monozygotic twins discordant for congenital heart defects
MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. Recent studies demonstrated that miRNAs are involved in the development of congenital heart defects (CHD). In this study, we aimed at identifying the specific patterns of miRNAs in blood of monozygotic twin pairs di...
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Published in: | PloS one 2019-12, Vol.14 (12), p.e0226164-e0226164 |
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creator | Abu-Halima, Masood Weidinger, Josephin Poryo, Martin Henn, Dominic Keller, Andreas Meese, Eckart Abdul-Khaliq, Hashim |
description | MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. Recent studies demonstrated that miRNAs are involved in the development of congenital heart defects (CHD). In this study, we aimed at identifying the specific patterns of miRNAs in blood of monozygotic twin pairs discordant for CHD and to assess whether miRNAs might be involved in the development or reflect the consequences of CHD.
miRNA microarray analysis and Real-Time Quantitative PCR (RT-qPCR) were employed to determine the miRNA abundance level from 12 monozygotic twins discordant for CHD and their non-CHD co-twins (n = 12). Enrichment analyses of altered miRNAs were performed using bioinformatics tools.
Compared with non-CHD co-twins, profiling analysis indicated 34 miRNAs with a significant difference in abundance level (p |
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miRNA microarray analysis and Real-Time Quantitative PCR (RT-qPCR) were employed to determine the miRNA abundance level from 12 monozygotic twins discordant for CHD and their non-CHD co-twins (n = 12). Enrichment analyses of altered miRNAs were performed using bioinformatics tools.
Compared with non-CHD co-twins, profiling analysis indicated 34 miRNAs with a significant difference in abundance level (p<0.05, fold change ≥ 1.3), of which 11 miRNAs were up-regulated and 23 miRNAs were down-regulated. Seven miRNAs were validated with RT-qPCR including miR-511-3p, miR-1306-5p, miR-421, miR-4707-3p, miR-4732-3p, miR-5189-3p, and miR-890, and the results were consistent with microarray analysis. Five miRNAs namely miR-511-3p, miR-1306-5p, miR-4732-3p, miR-5189-3p, and miR-890 were found to be significantly up-regulated in twins < 10 years old. Bioinformatics analysis showed that the 7 validated miRNAs were involved in phosphatidylinositol signaling, gap junction signaling, and adrenergic signaling in cardiomyocytes.
Our data show deregulated miRNA abundance levels in the peripheral blood of monozygotic twins discordant for CHD, and identify new candidates for further analysis, which may contribute to understanding the development of CHD in the future. Bioinformatics analysis indicated that the target genes of these miRNAs are likely involved in signaling and communication of cardiomyocytes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0226164</identifier><identifier>PMID: 31805172</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abundance ; Adolescent ; Bioinformatics ; Biology and life sciences ; Blood ; Cardiology ; Cardiomyocytes ; Case-Control Studies ; Child ; Defects ; Deoxyribonucleic acid ; Deregulation ; Diseases in Twins - genetics ; DNA ; DNA microarrays ; Female ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation ; Heart attacks ; Heart Defects, Congenital - genetics ; Heart failure ; Humans ; Medicine and Health Sciences ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Oligonucleotide Array Sequence Analysis ; Pediatrics ; Peripheral blood ; Phosphatidylinositol ; Post-transcription ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; Sequence Analysis, RNA ; Signaling ; Twins ; Twins, Monozygotic - genetics ; Young Adult</subject><ispartof>PloS one, 2019-12, Vol.14 (12), p.e0226164-e0226164</ispartof><rights>2019 Abu-Halima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Abu-Halima et al 2019 Abu-Halima et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-e19208f27d8442bd8ce7ca8f254d5c742bc33faa89a7de80dd4a7e607dda6b443</citedby><cites>FETCH-LOGICAL-c526t-e19208f27d8442bd8ce7ca8f254d5c742bc33faa89a7de80dd4a7e607dda6b443</cites><orcidid>0000-0001-9048-4958</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2322136563/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2322136563?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,74998</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31805172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Pulakat, Lakshmi</contributor><creatorcontrib>Abu-Halima, Masood</creatorcontrib><creatorcontrib>Weidinger, Josephin</creatorcontrib><creatorcontrib>Poryo, Martin</creatorcontrib><creatorcontrib>Henn, Dominic</creatorcontrib><creatorcontrib>Keller, Andreas</creatorcontrib><creatorcontrib>Meese, Eckart</creatorcontrib><creatorcontrib>Abdul-Khaliq, Hashim</creatorcontrib><title>Micro-RNA signatures in monozygotic twins discordant for congenital heart defects</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. Recent studies demonstrated that miRNAs are involved in the development of congenital heart defects (CHD). In this study, we aimed at identifying the specific patterns of miRNAs in blood of monozygotic twin pairs discordant for CHD and to assess whether miRNAs might be involved in the development or reflect the consequences of CHD.
miRNA microarray analysis and Real-Time Quantitative PCR (RT-qPCR) were employed to determine the miRNA abundance level from 12 monozygotic twins discordant for CHD and their non-CHD co-twins (n = 12). Enrichment analyses of altered miRNAs were performed using bioinformatics tools.
Compared with non-CHD co-twins, profiling analysis indicated 34 miRNAs with a significant difference in abundance level (p<0.05, fold change ≥ 1.3), of which 11 miRNAs were up-regulated and 23 miRNAs were down-regulated. Seven miRNAs were validated with RT-qPCR including miR-511-3p, miR-1306-5p, miR-421, miR-4707-3p, miR-4732-3p, miR-5189-3p, and miR-890, and the results were consistent with microarray analysis. Five miRNAs namely miR-511-3p, miR-1306-5p, miR-4732-3p, miR-5189-3p, and miR-890 were found to be significantly up-regulated in twins < 10 years old. Bioinformatics analysis showed that the 7 validated miRNAs were involved in phosphatidylinositol signaling, gap junction signaling, and adrenergic signaling in cardiomyocytes.
Our data show deregulated miRNA abundance levels in the peripheral blood of monozygotic twins discordant for CHD, and identify new candidates for further analysis, which may contribute to understanding the development of CHD in the future. Bioinformatics analysis indicated that the target genes of these miRNAs are likely involved in signaling and communication of cardiomyocytes.</description><subject>Abundance</subject><subject>Adolescent</subject><subject>Bioinformatics</subject><subject>Biology and life sciences</subject><subject>Blood</subject><subject>Cardiology</subject><subject>Cardiomyocytes</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Defects</subject><subject>Deoxyribonucleic acid</subject><subject>Deregulation</subject><subject>Diseases in Twins - genetics</subject><subject>DNA</subject><subject>DNA microarrays</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation</subject><subject>Heart attacks</subject><subject>Heart Defects, Congenital - genetics</subject><subject>Heart failure</subject><subject>Humans</subject><subject>Medicine and Health Sciences</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pediatrics</subject><subject>Peripheral blood</subject><subject>Phosphatidylinositol</subject><subject>Post-transcription</subject><subject>Research and Analysis Methods</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Sequence Analysis, RNA</subject><subject>Signaling</subject><subject>Twins</subject><subject>Twins, Monozygotic - genetics</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAUjBAVLYV_gCBSL1yy-Cu2c0GqKqCV2iKqcrYc-yX1KmsvtgMqvx6XTasWcbL1PDNv3vNU1RuMVpgK_GEd5uj1tNoGDytECMecPasOcEdJwwmizx_d96uXKa0Raqnk_EW1T7FELRbkoPp24UwMzdXlcZ3c6HWeI6Ta-XoTfPh9O4bsTJ1_OZ9q65IJ0Wqf6yHE2gQ_gndZT_UN6JhrCwOYnF5Ve4OeErxezsPq--dP1yenzfnXL2cnx-eNaQnPDeCOIDkQYSVjpLfSgDC6FFpmWyNKyVA6aC07LSxIZC3TAjgS1mreM0YPq3c73e0Uklq2kRShhGDKW04L4myHsEGv1Ta6jY63Kmin_hZCHFXx7cwEylAptAFguGMME95TgvQgSI-NNEPfFa2PS7e534A14HPU0xPRpy_e3agx_FRcdkxSWQTeLwIx_JghZbUp-4Rp0h7CvPMtMGOdKNCjf6D_n47tUOX_UoowPJjBSN0l5J6l7hKiloQU2tvHgzyQ7iNB_wA1GbsM</recordid><startdate>20191205</startdate><enddate>20191205</enddate><creator>Abu-Halima, Masood</creator><creator>Weidinger, Josephin</creator><creator>Poryo, Martin</creator><creator>Henn, Dominic</creator><creator>Keller, Andreas</creator><creator>Meese, Eckart</creator><creator>Abdul-Khaliq, Hashim</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-9048-4958</orcidid></search><sort><creationdate>20191205</creationdate><title>Micro-RNA signatures in monozygotic twins discordant for congenital heart defects</title><author>Abu-Halima, Masood ; Weidinger, Josephin ; Poryo, Martin ; Henn, Dominic ; Keller, Andreas ; Meese, Eckart ; Abdul-Khaliq, Hashim</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-e19208f27d8442bd8ce7ca8f254d5c742bc33faa89a7de80dd4a7e607dda6b443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Abundance</topic><topic>Adolescent</topic><topic>Bioinformatics</topic><topic>Biology and life sciences</topic><topic>Blood</topic><topic>Cardiology</topic><topic>Cardiomyocytes</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Defects</topic><topic>Deoxyribonucleic acid</topic><topic>Deregulation</topic><topic>Diseases in Twins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abu-Halima, Masood</au><au>Weidinger, Josephin</au><au>Poryo, Martin</au><au>Henn, Dominic</au><au>Keller, Andreas</au><au>Meese, Eckart</au><au>Abdul-Khaliq, Hashim</au><au>Pulakat, Lakshmi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Micro-RNA signatures in monozygotic twins discordant for congenital heart defects</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-12-05</date><risdate>2019</risdate><volume>14</volume><issue>12</issue><spage>e0226164</spage><epage>e0226164</epage><pages>e0226164-e0226164</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. Recent studies demonstrated that miRNAs are involved in the development of congenital heart defects (CHD). In this study, we aimed at identifying the specific patterns of miRNAs in blood of monozygotic twin pairs discordant for CHD and to assess whether miRNAs might be involved in the development or reflect the consequences of CHD.
miRNA microarray analysis and Real-Time Quantitative PCR (RT-qPCR) were employed to determine the miRNA abundance level from 12 monozygotic twins discordant for CHD and their non-CHD co-twins (n = 12). Enrichment analyses of altered miRNAs were performed using bioinformatics tools.
Compared with non-CHD co-twins, profiling analysis indicated 34 miRNAs with a significant difference in abundance level (p<0.05, fold change ≥ 1.3), of which 11 miRNAs were up-regulated and 23 miRNAs were down-regulated. Seven miRNAs were validated with RT-qPCR including miR-511-3p, miR-1306-5p, miR-421, miR-4707-3p, miR-4732-3p, miR-5189-3p, and miR-890, and the results were consistent with microarray analysis. Five miRNAs namely miR-511-3p, miR-1306-5p, miR-4732-3p, miR-5189-3p, and miR-890 were found to be significantly up-regulated in twins < 10 years old. Bioinformatics analysis showed that the 7 validated miRNAs were involved in phosphatidylinositol signaling, gap junction signaling, and adrenergic signaling in cardiomyocytes.
Our data show deregulated miRNA abundance levels in the peripheral blood of monozygotic twins discordant for CHD, and identify new candidates for further analysis, which may contribute to understanding the development of CHD in the future. Bioinformatics analysis indicated that the target genes of these miRNAs are likely involved in signaling and communication of cardiomyocytes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31805172</pmid><doi>10.1371/journal.pone.0226164</doi><orcidid>https://orcid.org/0000-0001-9048-4958</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Abundance Adolescent Bioinformatics Biology and life sciences Blood Cardiology Cardiomyocytes Case-Control Studies Child Defects Deoxyribonucleic acid Deregulation Diseases in Twins - genetics DNA DNA microarrays Female Gene expression Gene Expression Profiling - methods Gene Expression Regulation Heart attacks Heart Defects, Congenital - genetics Heart failure Humans Medicine and Health Sciences MicroRNAs MicroRNAs - genetics miRNA Oligonucleotide Array Sequence Analysis Pediatrics Peripheral blood Phosphatidylinositol Post-transcription Research and Analysis Methods Ribonucleic acid RNA Sequence Analysis, RNA Signaling Twins Twins, Monozygotic - genetics Young Adult |
title | Micro-RNA signatures in monozygotic twins discordant for congenital heart defects |
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