Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation
Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possib...
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| Veröffentlicht in: | PloS one 2015-08, Vol.10 (8), p.e0135737-e0135737 |
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| creator | Ng, Pak Cheung Chan, Kathy Yuen Yee Leung, Kam Tong Tam, Yuk Him Ma, Terence Ping Yuen Lam, Hugh Simon Cheung, Hon Ming Lee, Kim Hung To, Ka Fai Li, Karen |
| description | Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology.
We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples.
We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR-203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction.
The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology. |
| doi_str_mv | 10.1371/journal.pone.0135737 |
| format | Article |
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We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples.
We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR-203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction.
The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0135737</identifier><identifier>PMID: 26274503</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activator protein 1 ; Algorithms ; Angiogenesis ; Arginine ; Bioinformatics ; Biomarkers ; Cell adhesion ; Chemotaxis ; Comparative analysis ; Congenital diseases ; Cytotoxicity ; Enterocolitis ; Enterocolitis, Necrotizing - metabolism ; Enterocolitis, Necrotizing - pathology ; Extracellular matrix ; Female ; Gastrointestinal diseases ; Gene Expression Profiling ; Gene Expression Regulation ; Genomics ; Health aspects ; Hospitals ; Humans ; Hypoxia ; Infant, Newborn ; Infant, Premature ; Infants ; Inflammation ; Inflammatory bowel disease ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - pathology ; Intestinal perforation ; Intestinal Perforation - metabolism ; Intestinal Perforation - pathology ; Intestine ; Intestine, Small - metabolism ; Intestine, Small - pathology ; Lymphocytes T ; Male ; Metabolism ; MicroRNA ; MicroRNAs ; MicroRNAs - biosynthesis ; miRNA ; Molecular chains ; Molecular modelling ; Morbidity ; Mortality ; Mucosa ; Muscle contraction ; Muscles ; Necrosis ; Necrotizing enterocolitis ; Newborn babies ; Ostomy ; Oxidative stress ; Perforation ; Premature infants ; Proteins ; Signal transduction ; Small intestine ; Surgery ; T cells ; Tissues ; TLR4 protein ; Toll-like receptors ; Transcription factors</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0135737-e0135737</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Ng 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>2015 Ng et al 2015 Ng et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-9bf496062490d47ff5e9d79fd7f95efdef062a016ee59e219256f08fe2a351e63</citedby><cites>FETCH-LOGICAL-c692t-9bf496062490d47ff5e9d79fd7f95efdef062a016ee59e219256f08fe2a351e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537110/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537110/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2919,23857,27915,27916,53782,53784,79361,79362</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26274503$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Neu, Josef</contributor><creatorcontrib>Ng, Pak Cheung</creatorcontrib><creatorcontrib>Chan, Kathy Yuen Yee</creatorcontrib><creatorcontrib>Leung, Kam Tong</creatorcontrib><creatorcontrib>Tam, Yuk Him</creatorcontrib><creatorcontrib>Ma, Terence Ping Yuen</creatorcontrib><creatorcontrib>Lam, Hugh Simon</creatorcontrib><creatorcontrib>Cheung, Hon Ming</creatorcontrib><creatorcontrib>Lee, Kim Hung</creatorcontrib><creatorcontrib>To, Ka Fai</creatorcontrib><creatorcontrib>Li, Karen</creatorcontrib><title>Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology.
We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples.
We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR-203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction.
The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology.</description><subject>Activator protein 1</subject><subject>Algorithms</subject><subject>Angiogenesis</subject><subject>Arginine</subject><subject>Bioinformatics</subject><subject>Biomarkers</subject><subject>Cell adhesion</subject><subject>Chemotaxis</subject><subject>Comparative analysis</subject><subject>Congenital diseases</subject><subject>Cytotoxicity</subject><subject>Enterocolitis</subject><subject>Enterocolitis, Necrotizing - metabolism</subject><subject>Enterocolitis, Necrotizing - pathology</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Gastrointestinal diseases</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Infant, Newborn</subject><subject>Infant, Premature</subject><subject>Infants</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - pathology</subject><subject>Intestinal perforation</subject><subject>Intestinal Perforation - metabolism</subject><subject>Intestinal Perforation - pathology</subject><subject>Intestine</subject><subject>Intestine, Small - metabolism</subject><subject>Intestine, Small - pathology</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Metabolism</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - biosynthesis</subject><subject>miRNA</subject><subject>Molecular chains</subject><subject>Molecular modelling</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Mucosa</subject><subject>Muscle contraction</subject><subject>Muscles</subject><subject>Necrosis</subject><subject>Necrotizing enterocolitis</subject><subject>Newborn babies</subject><subject>Ostomy</subject><subject>Oxidative stress</subject><subject>Perforation</subject><subject>Premature infants</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Small intestine</subject><subject>Surgery</subject><subject>T cells</subject><subject>Tissues</subject><subject>TLR4 protein</subject><subject>Toll-like receptors</subject><subject>Transcription 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ng, Pak Cheung</au><au>Chan, Kathy Yuen Yee</au><au>Leung, Kam Tong</au><au>Tam, Yuk Him</au><au>Ma, Terence Ping Yuen</au><au>Lam, Hugh Simon</au><au>Cheung, Hon Ming</au><au>Lee, Kim Hung</au><au>To, Ka Fai</au><au>Li, Karen</au><au>Neu, Josef</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-14</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0135737</spage><epage>e0135737</epage><pages>e0135737-e0135737</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology.
We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples.
We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR-203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction.
The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26274503</pmid><doi>10.1371/journal.pone.0135737</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-08, Vol.10 (8), p.e0135737-e0135737 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1705057711 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); PubMed (Medline); EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Activator protein 1 Algorithms Angiogenesis Arginine Bioinformatics Biomarkers Cell adhesion Chemotaxis Comparative analysis Congenital diseases Cytotoxicity Enterocolitis Enterocolitis, Necrotizing - metabolism Enterocolitis, Necrotizing - pathology Extracellular matrix Female Gastrointestinal diseases Gene Expression Profiling Gene Expression Regulation Genomics Health aspects Hospitals Humans Hypoxia Infant, Newborn Infant, Premature Infants Inflammation Inflammatory bowel disease Intestinal Mucosa - metabolism Intestinal Mucosa - pathology Intestinal perforation Intestinal Perforation - metabolism Intestinal Perforation - pathology Intestine Intestine, Small - metabolism Intestine, Small - pathology Lymphocytes T Male Metabolism MicroRNA MicroRNAs MicroRNAs - biosynthesis miRNA Molecular chains Molecular modelling Morbidity Mortality Mucosa Muscle contraction Muscles Necrosis Necrotizing enterocolitis Newborn babies Ostomy Oxidative stress Perforation Premature infants Proteins Signal transduction Small intestine Surgery T cells Tissues TLR4 protein Toll-like receptors Transcription factors |
| title | Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation |
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